Cross-linking agent(s)

ABSTRACT

Cross-linking agent(s), composition(s) made therefrom and use(s) thereof. For example, crosslinking agent(s) that are used to make composition(s) such as hydrogel material(s). Such materials are useful in the manufacture of biocompatible medical devices, for example, hydrogel materials having desirable physical properties for use as contact lense(s) and/or stimulating device(s).

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.16/323,818, filed Feb. 7, 2019, now U.S. Pat. No. 10,919,853 issued Feb.16, 2021. U.S. application Ser. No. 16/323,818 is the 35 U.S.C. § 371national stage application of PCT Application No. PCT/CA2017/050933,filed Aug. 4, 2017, where the PCT claims the priority to and benefit ofU.S. Provisional Patent Application No. 62/372,537, filed Aug. 9, 2016.Each of these applications is incorporated herein by reference in theirentireties.

FIELD

The subject application relates generally to cross-linking agent(s),composition(s) made therefrom and use(s) thereof. For example, theapplication is directed to crosslinking agent(s) that are used to makecomposition(s) such as hydrogel material(s). Such materials are usefulin the manufacture of biocompatible medical devices, for example,hydrogel materials, which include silicon hydrogels, having desirablephysical properties for use as contact lense(s) and/or stimulatingdevice(s).

BACKGROUND

Hydrogels are hydrophilic polymers that absorb water, and areessentially insoluble in water at physiologic temperature, pH, and ionicstrength due to the presence of a three-dimensional polymeric network.While hydrogel are prepared from hydrophilic monomers, hydrophobicmonomer are sometimes used in hydrogel preparation in order to regulatethe properties of specific applications. The three-dimensional networkincludes crosslinks between polymer chains of the network, and thesecrosslinks can be formed by covalent bonds, electrostatic, hydrophobic,or dipole-dipole interactions. The hydrophilicity of the hydrogelmaterials is in large part due to the presence of hydrophilic groups, insome instances, along the polymer backbone, and in other instances, asfunctional side groups that extend from the polymer backbone. Generally,a hydrogel is a crosslinked polymer that absorbs water to an equilibriumvalue of at least 10% water. The water-swollen equilibrated state of ahydrogel results from a balance between an osmotic force that drives thewater to enter the hydrophilic polymer network, and a cohesive forceexerted by the polymer chains in resisting expansion. In some fashion,both the osmotic force and the cohesive force correlates with the typeof monomers used to prepare the hydrogel polymeric material and thecrosslink density of the polymeric hydrogel material. In general, aperson of ordinary skill would expect a greater degree of crosslinkingfor a given hydrogel polymeric material will result in a correspondingdecrease in water content, i.e., at equilibrium, the weight percentageof water absorbed by the polymeric network under physiologicalconditions relative to its total (dry plus water) weight. Water content(%) is simply {[wet lens (g)−dry lens (g)]/wet lens (g)}×100 atequilibrium.

Hydrogels can be classified as synthetic or natural according to theirorigin; degradable or stable depending on their stabilitycharacteristics, and intelligent or conventional depending on theirability to exhibit significant dimensional changes with variations inpH, temperature or electric field. One class of conventional synthetichydrogels is prepared by free-radical polymerization of vinyl or(meth)acrylate monomers using thermal or photo initiators. Severalimportant classes of monomers are recognized by persons of skill with aninterest to prepare hydrogel polymeric materials. There are the neutralmonomers, for example, methacrylates and acrylates, e.g., 2-hydroxyethylmethacrylate (HEMA), acrylamide/methacrylamides, e.g., dimethylacrylamide (DMA), glycerol methacrylate (GMA) and cyclic lactams, e.g.,N-vinyl-2-pyrrolidone (NVP). At times, the term N-vinylpyrrolidone isused interchangeably with N-vinyl-2-pyrrolidone, and both chemical termsare well recognized by persons of ordinary skill to mean the same vinylmonomer. Another class of monomers is the ionic or charged (underphysiological conditions) monomers, including, methacrylic acid, acrylicacid, methylpropylsulfonic acid and p-styrene sulfonate. Typically, inthe making of contact lenses the ionic class of monomer is present atlow concentration relative to the neutral class of monomer, but theformer can have a dramatic effect on water content of the material. Forexample, copolymerization of 2% w/w methacrylic acid with HEMA resultsin a hydrogel possessing a water content of 60% (compared with 38% watercontent for HEMA alone). As used herein “(meth)” refers to an optionalmethyl substitution. Thus, a term such as “(meth)acrylate” denotes bothmethacrylic and acrylic radicals.

Hydrogel materials prepared with vinyl cyclic lactams. e.g.,N-vinyl-2-pyrrolidone (NVP) can have relatively high water content, andthus, an acceptable level of oxygen permeability. For example, NVP isoften copolymerized with an alkyl acrylate or methacrylate such asmethyl methacrylate to provide lens materials that typically have awater content of 50% to 80% by weight. However, such copolymers aredifficult to synthesize in a controlled manner because of the differencein their respective rates of polymerization between the N-vinyl groupsof NVP and the acryloyl or methacryloyl groups of the alkyl acrylate ormethacrylate. During free-radical polymerization, the methacrylatemonomers polymerize relatively quickly while the vinyl cyclic lactammonomer polymerize more slowly, and therefore, only small amounts of thetwo co-monomers actually react with the other. What one finds is thatthe polymer network is essentially an interpenetrating network ofpoly(vinyl monomer) and poly((meth)acrylate)). The result is often aphase separation and a corresponding decrease in the transparency of thepolymeric lens material, or the mechanical properties of the lensmaterial deteriorates as the lens absorbs water.

It is also observed, and not to be overlooked, that in a conventionalpoly(vinyl monomer) and poly((meth)acrylate)) hydrogel framework aminimum of crosslinking occurs between the two essentially homopolymers.In the absence of a suitable crosslinking agent to link the two dualphase polymers, high levels of extractables and dimensional instabilityresults. There have been attempts to design crosslinking agents thataddress this technical issue. See, U.S. Pat. No. 5,449,729 (Lai, et al),which discloses the use of a crosslinking agent containing bothmethacrylate and vinyl carbonate reactivity. However, technical issuessuch as cost to synthesize, toxic preparatory chemistry as well as therelative instability of the vinyl carbonate functionality has limitedthe development of this dual reactive cross-linking agent(s).

There have been attempts to prepare high water content hydrogels usingtwo different cross-linking agent(s), i.e., allyl methacrylate (AMA) ordivinylethylene urea (DVEU), to incorporate the vinyl (cyclic lactam)monomer into the hydrogel polymer network. The AMA cross-linkingagent(s) works quite well with monomers systems where a fastpolymerizing (meth)acrylate are used and leaves the slow polymerizableNVP intact. The technical issue with AMA is that it is too volatile andcan volatilize during the thermal cure of the polymer resulting ininconsistent levels of crosslinking from one polymerization to the next.Also, DVEU is not an optimal crosslinking agent because it possesses towvinyl group with the same reactivity on the same molecule, and seems tolimit the mobility of the poly(NVP) within the hydrogel framework. Forexample, as films or lenses are being made, or as water enters theframework, the resulting hydrogel material can exhibit loss of lubricityat the surface of the hydrogel. For application of a contact lens, theloss of lubricity is believed to be detrimental to the sensed comfort aconsumer will experience in wearing the lens.

Silicone hydrogels combine the high oxygen permeability ofpolydimethylsiloxane and the excellent water absorption characteristicsof a hydrogel. However, for the application of a contact lens, one wellknown issue with preparing silicone hydrogels is that silicone basedmonomers are hydrophobic, and relatively, incompatible in regards toforming a homogeneous polymerization mixture with the hydrophilicmonomers present in the mixture. The copolymerization of (meth)acrylatefunctionalized silicones with hydrophilic monomers generally results inopaque, phase separated materials. Technical approaches to minimize suchmix incompatibility can include the use of a solubilizing co-solvent orincorporating hydrophilic groups to the silicone backbone.

There is still a need for components and/or materials useful for makingbiocompatible medical devices that have desired physical properties.

SUMMARY

In accordance with an aspect, there is a compound of formula I:

-   -   R¹-R¹¹ are the same or different, and are each independently        selected from H, halo, hydroxyl, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, a substituted or unsubstituted        heteroaromatic group, or NR^(a)R^(b), wherein R^(a) and R^(b)        are the same or different, and are independently selected from        H, halo, hydroxyl, amino, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, or a substituted or        unsubstituted heteroaromatic group;    -   X¹ and X² are the same or different, and are each independently        selected from a direct bond, a heteroatom, C(O), a substituted        or unsubstituted hydrocarbon group, a substituted or        unsubstituted heterogeneous group, a substituted or        unsubstituted carbocyclic group, a substituted or unsubstituted        heterocyclic group, a substituted or unsubstituted aromatic        group, a substituted or unsubstituted heteroaromatic group, or        NR^(a); and    -   Z is selected from a heteroatom, C(O), a substituted or        unsubstituted hydrocarbon group, a substituted or unsubstituted        heterogeneous group, a substituted or unsubstituted carbocyclic        group, a substituted or unsubstituted heterocyclic group, a        substituted or unsubstituted aromatic group, a substituted or        unsubstituted heteroaromatic group, NR^(a), or        [SiR¹²R¹³O]_(w)SiR¹²R¹³, wherein R¹² and R¹³ are the same or        different, and are independently selected from H, halo,        hydroxyl, amino, a substituted or unsubstituted hydrocarbon        group, a substituted or unsubstituted heterogeneous group, a        substituted or unsubstituted carbocyclic group, a substituted or        unsubstituted heterocyclic group, a substituted or unsubstituted        aromatic group, or a substituted or unsubstituted heteroaromatic        group, and w is from 0 to 60.

In another aspect, there is provided a compound of formula II:

-   -   R¹-R¹¹ are the same or different, and are each independently        selected from H, halo, hydroxyl, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, a substituted or unsubstituted        heteroaromatic group, or NR^(a)R^(b), wherein R^(a) and R^(b)        are the same or different, and are independently selected from        H, halo, hydroxyl, amino, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, or a substituted or        unsubstituted heteroaromatic group;    -   X¹ and X² are the same or different, and are each independently        selected from a direct bond, a heteroatom, C(O), a substituted        or unsubstituted hydrocarbon group, a substituted or        unsubstituted heterogeneous group, a substituted or        unsubstituted carbocyclic group, a substituted or unsubstituted        heterocyclic group, a substituted or unsubstituted aromatic        group, a substituted or unsubstituted heteroaromatic group, or        NR^(a); and    -   Z is selected from a heteroatom, C(O), a substituted or        unsubstituted hydrocarbon group, a substituted or unsubstituted        heterogeneous group, a substituted or unsubstituted carbocyclic        group, a substituted or unsubstituted heterocyclic group, a        substituted or unsubstituted aromatic group, a substituted or        unsubstituted heteroaromatic group, NR^(a), or        [SiR¹²R¹³O]_(w)SiR¹²R¹³, wherein R¹² and R¹³ are the same or        different, and are independently selected from H, halo,        hydroxyl, amino, a substituted or unsubstituted hydrocarbon        group, a substituted or unsubstituted heterogeneous group, a        substituted or unsubstituted carbocyclic group, a substituted or        unsubstituted heterocyclic group, a substituted or unsubstituted        aromatic group, or a substituted or unsubstituted heteroaromatic        group, and w is from 0 to 60.

In other aspects described herein, wherein R¹-R¹¹ are the same ordifferent, and are each independently selected from H, halo, hydroxyl, asubstituted or unsubstituted hydrocarbon group, or a substituted orunsubstituted heterogeneous group. In further aspects, wherein R¹-R¹¹are the same or different, and are each independently selected from H,halo, hydroxyl, a substituted or unsubstituted C₁-C₆ alkyl, asubstituted or unsubstituted C₁-C₆ alkoxy, or a substituted orunsubstituted C₁-C₆ alkanol. In other aspects, wherein R¹-R¹¹ are thesame or different, and are each independently selected from H or asubstituted or unsubstituted hydrocarbon group. In further aspects,wherein R¹-R¹¹ are the same or different, and are each independentlyselected from H or a substituted or unsubstituted alkyl group. In otheraspects, wherein R¹-R¹¹ are the same or different, and are eachindependently selected from H or a substituted or unsubstituted C₁-C₆alkyl. In yet other aspects, wherein R¹-R¹¹ are the same or different,and are each independently selected from H or unsubstituted C₁-C₆ alkyl.In further aspects wherein R¹-R¹¹ are the same or different, and areeach independently selected from H or methyl. In other aspects, whereinR¹, R², R¹⁰, and R¹¹ are H.

In other aspects described herein, wherein X¹ and X² are the same ordifferent, and are each independently selected from a direct bond, O,NR^(a), C(O), C(O)NR^(a), NR^(a)C(O), OC(O)NR^(a), NR^(a)C(O)O,NR^(a)C(O)NH, NHC(O)NR^(a), C(O)O, OC(O), NHC(O)NHZ₀—NH—C(O)NH,OC(O)NHZ₀—NH—C(O)O, OC(O)NHZ₀—NH—C(O)NH, or NHC(O)NHZ₀—NH—C(O)O; whereZ₀ is a linear or branched C₂-C₁₂ alkylene divalent radical, or a C₅-C₇cycloaliphatic divalent radical, each of which can optionally includeone or more linkages of O, NR^(a) and C(O). In further aspects, whereinX¹ and X² are the same or different, and are each independently selectedfrom a direct bond, O, NR^(a), C(O), C(O)NR^(a), NR^(a)C(O), NR^(a)C(O),OC(O)NR^(a), NR^(a)C(O)O, C(O)O, or OC(O). In other aspects, whereinR^(a) is selected from H or a substituted or unsubstituted hydrocarbongroup. In further aspects, wherein R^(a) is selected from H orunsubstituted C₁-C₆ alkyl. In other aspects, wherein R^(a) is selectedfrom H or methyl. In further aspects, wherein X¹ and X² are the same ordifferent, and are each independently selected from a direct bond, O, orNR^(a).

In other aspects described herein, wherein Z is selected from a directbond, a substituted or unsubstituted hydrocarbon group, a substituted orunsubstituted heterogeneous group, or [SiR¹²R¹³O]_(w)SiR¹²R¹³. In otheraspects, wherein Z is selected from a direct bond, a substituted orunsubstituted hydrocarbon group, a substituted or unsubstitutedheterogeneous group, or [SiR¹²R¹³O]_(w)SiR¹²R¹³, wherein R¹² and R¹³ arethe same or different, and are independently selected from C₁-C₄ alkylor phenyl, and w is from 0 to 60. In further aspects, wherein Z isselected from a direct bond, or a substituted or unsubstitutedhydrocarbon group. In other aspects, wherein Z is selected from asubstituted or unsubstituted hydrocarbon group. In further aspects,wherein Z is selected from a substituted or unsubstituted alkyl group.In other aspects, wherein Z is selected from a substituted orunsubstituted C₁-C₂₀ alkyl. In further aspects, wherein Z is selectedfrom a substituted or unsubstituted C₁-C₆ alkyl. In other aspects,wherein Z is selected from an unsubstituted C₁-C₆ alkyl. In furtheraspects, wherein Z is selected from a substituted or unsubstitutedaromatic group. In other aspects, wherein Z is selected from asubstituted or unsubstituted phenyl group. In further aspects, wherein Zis selected from a C₁-C₁₂ unsubstituted or substituted, linear orbranched alkylene divalent radical, where each alkylene divalent radicalcan optionally include one or more linkages of O, NR^(a), and C(O), anunsubstituted phenylene divalent radical, a C₅-C₇ cycloaliphaticdivalent radical, or a C₇-C₁₂ arylalkylene divalent radical.

In other aspects described herein, wherein the compound is Formula III

In other aspects described herein, wherein the compound is selected fromone or more of

In other aspects described herein, wherein —X¹—Z—X²— is not—CH₂—CH₂—O—C(O)—.

In other aspects described herein, wherein the compound is not

In other aspects described herein, wherein the compound is a dualreactive cross-linking agent(s).

In other aspects described herein, there is provided a compositioncomprising one or more of the compounds defined herein.

In other aspects described herein, there is provided use of one or moreof the compounds defined herein.

In other aspects described herein, there is provided use of one or moreof the compounds defined herein to produce biocompatible medicaldevices(s).

In other aspects described herein, there is provided a method ofproducing biocompatible medical devices(s), the method comprisingreacting at least one of the compounds defined herein with at least onemonomer.

In other aspects described herein, there is provided a compositioncomprising at least one (meth)acrylic monomer, at least one vinylcontaining monomer and at least one of the compounds as defined herein.

In other aspects described herein, wherein the at least one vinylcontaining monomer comprises at least one silicone monomer. In otheraspects, wherein the silicone monomer is selected from the groupconsisting of tris-(trimethylsiloxy)-3-methacryloxypropyl methacrylate(Tris), 3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane (Sigma), or a mixture thereof.In further aspects, wherein the at least one vinyl containing monomer isselected from hydroxyethylmethacrylate (HEMA), glycidyl methacrylate(GMMA), dimethylacrylamide (DMA), 3-(tris-(trimethylsiloxy)silyl)propylmethacrylate (TRIS), hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane (SIGMA), or combinations thereof. In other aspects, whereinthe at least one vinyl monomer is selected from N-vinyl-2-pyrrolidone,N-vinyl piperidone, N-vinyl-caprolactam, N-vinylimidazolidone,N-vinylsuccinimide, N-vinylformamide, N-vinyl urea, N-vinylcarbamate,O-vinyl carbonate, or combinations thereof. In further aspects, whereinthe at least one (meth)acrylic monomer includes4-t-butyl-2-hydroxycyclohexylmethacrylate, and the at least one vinylmonomer includes N-vinyl-2-pyrrolidone. In other aspects, wherein the atleast one (meth)acrylic monomer includes a functional monomer selectedfrom the group consisting of carboxybetaines, sulfobetains andphosphobetaines. In other aspects, wherein the functional monomer isselected from the group consisting of methacryloxy phosphatidyl choline(MPC), N-vinylcarboxy ethyl phosphatidyl choline, O-vinyl ethylphosphatidyl choline carbonate, 1-(3-sulfopropyl)-2-vinylpyridiniumbetaine, and 3-dimethyl(acryloyloxyethyl) ammonium propyl sulfonate. Inother aspects, further comprising at least one photoinitiator. Infurther aspects, further comprising at least one (meth)acrylatecross-linking agent. In other aspects, wherein the Tris, Sigma or thecombination thereof is present from about 8% to about 30% by weight. Infurther aspects, wherein the at least one compound is present from about0.02% to about 0.4% by weight.

In other aspects described herein, there is provided a hydrogel polymerprepared from the composition described herein. In other aspects,wherein the polymer possesses a water content of at least about 40% byweight, at least about 45% by weight, at least about 50% by weight, atleast about 65% by weight, at least about 70% by weight, at least about71% by weight, at least about 77% by weight, or at least about 80% byweight. In further aspects, wherein the polymer possesses a modulus ofelasticity of at least about 0.30 MPa, at least about 0.35 MPa, at leastabout 0.40 MPa, or at least about 0.45 MPa.

In other aspects described herein, there is provided a contact lensprepared with the hydrogel polymer described herein.

Other features and advantages of the present invention will becomeapparent from the following detailed description. It should beunderstood, however, that the detailed description and the specificexamples while indicating embodiments of the invention are given by wayof illustration only, since various changes and modifications within thespirit and scope of the invention will become apparent to those skilledin the art from the detailed description.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS Definitions

When describing the compounds, compositions, methods and uses of thisinvention, the following terms have the following meanings unlessotherwise indicated.

The compounds of the present invention may have asymmetric centers,chiral axes, and chiral planes (as described, for example, in: E. L.Eliel and S. H. Wilen, Stereo-chemistry of Carbon Compounds, John Wiley& Sons, New York, 1994, pages 1119-1190), and occur as racemates,racemic mixtures, and as individual diastereomers, with all possibleisomers and mixtures thereof, including optical isomers, E isomers, andZ isomers, being included in the present invention. In addition, thecompounds disclosed herein may exist as tautomers and both tautomericforms are intended to be encompassed by the scope of the invention, eventhough only one tautomeric structure may be depicted.

Generally, reference to a certain element such as hydrogen or H is meantto, if appropriate, include all isotopes of that element.

Where the term “alkyl group” is used, either alone or within other termssuch as “haloalkyl group” and “alkylamino group”, it encompasses linearor branched carbon radicals having, for example, one to about twentycarbon atoms or, in specific embodiments, one to about twelve carbonatoms. In other embodiments, alkyl groups are “lower alkyl” groupshaving one to about six carbon atoms. Examples of such groups include,but are not limited thereto, methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl andthe like. In more specific embodiments, lower alkyl groups have one tofour carbon atoms.

The term “alkenyl group” encompasses linear or branched carbon radicalshaving at least one carbon-carbon double bond. The term “alkenyl group”can encompass conjugated and non-conjugated carbon-carbon double bondsor combinations thereof. An alkenyl group, for example and without beinglimited thereto, can encompass two to about twenty carbon atoms or, in aparticular embodiment, two to about twelve carbon atoms. In embodiments,alkenyl groups are “lower alkenyl” groups having two to about fourcarbon atoms. Examples of alkenyl groups include, but are not limitedthereto, ethenyl, propenyl, allyl, propenyl, butenyl and4-methylbutenyl. The terms “alkenyl group” and “lower alkenyl group”,encompass groups having “cis” and “trans” orientations, oralternatively, “E” and “Z” orientations.

The term “alkynyl group” denotes linear or branched carbon radicalshaving at least one carbon-carbon triple bond. The term “alkynyl group”can encompass conjugated and non-conjugated carbon-carbon triple bondsor combinations thereof. Alkynyl group, for example and without beinglimited thereto, can encompass two to about twenty carbon atoms or, in aparticular embodiment, two to about twelve carbon atoms. In embodiments,alkynyl groups are “lower alkynyl” groups having two to about ten carbonatoms. Some examples are lower alkynyl groups having two to about fourcarbon atoms. Examples of such groups include propargyl, butynyl, andthe like.

The term “halo” means halogens such as fluorine, chlorine, bromine oriodine atoms.

The term “haloalkyl group” encompasses groups wherein any one or more ofthe alkyl carbon atoms is substituted with halo as defined above.Specifically encompassed are monohaloalkyl, dihaloalkyl andpolyhaloalkyl groups including perhaloalkyl. A monohaloalkyl group, forone example, may have either an iodo, bromo, chloro or fluoro atomwithin the group. Dihalo and polyhaloalkyl groups may have two or moreof the same halo atoms or a combination of different halo groups. “Lowerhaloalkyl group” encompasses groups having 1-6 carbon atoms. In someembodiments, lower haloalkyl groups have one to three carbon atoms.Examples of haloalkyl groups include fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl anddichloropropyl.

The term “hydroxyalkyl group” encompasses linear or branched alkylgroups having, for example and without being limited thereto, one toabout ten carbon atoms, any one of which may be substituted with one ormore hydroxyl groups. In embodiments, hydroxyalkyl groups are “lowerhydroxyalkyl” groups having one to six carbon atoms and one or morehydroxyl groups. Examples of such groups include hydroxymethyl,hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl.

The term “alkoxy group” encompasses linear or branched oxy-containinggroups each having alkyl portions of, for example and without beinglimited thereto, one to about ten carbon atoms. In embodiments, alkoxygroups are “lower alkoxy” groups having one to six carbon atoms.Examples of such groups include methoxy, ethoxy, propoxy, butoxy andtert-butoxy. In certain embodiments, lower alkoxy groups have one tothree carbon atoms. The “alkoxy” groups may be further substituted withone or more halo atoms, such as fluoro, chloro or bromo, to provide“haloalkoxy” groups. In other embodiments, lower haloalkoxy groups haveone to three carbon atoms. Examples of such groups includefluoromethoxy, chloromethoxy, trifluoromethoxy, trifluoroethoxy,fluoroethoxy, and fluoropropoxy.

The term “aromatic group” or “aryl group” means an aromatic group havingone or more rings wherein such rings may be attached together in apendent manner or may be fused. In particular embodiments, an aromaticgroup is one, two or three rings. Monocyclic aromatic groups may contain4 to 10 carbon atoms, typically 4 to 7 carbon atoms, and more typically4 to 6 carbon atoms in the ring. Typical polycyclic aromatic groups havetwo or three rings. Polycyclic aromatic groups having two ringstypically have 8 to 12 carbon atoms, typically 8 to 10 carbon atoms inthe rings. Examples of aromatic groups include, but are not limited to,phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl,anthryl or acenaphthyl.

The term “heteroatom” means an atom other than carbon. Typically,heteroatoms are selected from the group consisting of sulfur,phosphorous, nitrogen and oxygen atoms. Groups containing more than oneheteroatom may contain different heteroatoms.

The term “heteroaromatic group” or “heteroaryl group” means an aromaticgroup having one or more rings wherein such rings may be attachedtogether in a pendent manner or may be fused, wherein the aromatic grouphas at least one heteroatom. Monocyclic heteroaromatic groups maycontain 4 to 10 member atoms, typically 4 to 7 member atoms, and moretypically 4 to 6 member atoms in the ring. Typical polycyclicheteroaromatic groups have two or three rings. Polycyclic aromaticgroups having two rings typically have 8 to 12 member atoms, moretypically 8 to 10 member atoms in the rings. Examples of heteroaromaticgroups include, but are not limited thereto, pyrrole, imidazole,thiazole, oxazole, furan, thiophene, triazole, pyrazole, isoxazole,isothiazole, pyridine, pyrazine, pyridazine, pyrimidine, triazine,indole, benzofuran, benzothiophene, benzimidazole, benzthiazole,quinoline, isoquinoline, quinazoline, quinoxaline and the like.

The term “carbocyclic group” means a saturated or unsaturatedcarbocyclic hydrocarbon ring. Carbocyclic groups are not aromatic.Carbocyclic groups are monocyclic or polycyclic. Polycyclic carbocyclicgroups can be fused, spiro, or bridged ring systems. Monocycliccarbocyclic groups may contain 4 to 10 carbon atoms, typically 4 to 7carbon atoms, and more typically 5 to 6 carbon atoms in the ring.Bicyclic carbocyclic groups may contain 8 to 12 carbon atoms, typically9 to 10 carbon atoms in the rings.

The term “heterocyclic group” means a saturated or unsaturated ringstructure containing carbon atoms and 1 or more heteroatoms in the ring.Heterocyclic groups are not aromatic. Heterocyclic groups are monocyclicor polycyclic. Polycyclic heterocyclic groups can be fused, spiro, orbridged ring systems. Monocyclic heterocyclic groups may contain 4 to 10member atoms (i.e., including both carbon atoms and at least 1heteroatom), typically 4 to 7, and more typically 5 to 6 in the ring.Bicyclic heterocyclic groups may contain 8 to 18 member atoms, typically9 or 10 member atoms in the rings. Representative heterocyclic groupsinclude, by way of example, pyrrolidine, imidazolidine, pyrazolidine,piperidine, 1,4-dioxane, morpholine, thiomorpholine, piperazine,3-pyrroline and the like.

The term “heterogeneous group” means a saturated or unsaturated chain ofnon-hydrogen member atoms comprising carbon atoms and at least oneheteroatom. Heterogeneous groups typically have 1 to 25 member atoms.More typically, the chain contains 1 to 12 member atoms, 1 to 10, andmost typically 1 to 6. The chain may be linear or branched. Typicalbranched heterogeneous groups have one or two branches, more typicallyone branch. Typically, heterogeneous groups are saturated. Unsaturatedheterogeneous groups may have one or more double bonds, one or moretriple bonds, or both. Typical unsaturated heterogeneous groups have oneor two double bonds or one triple bond. More typically, the unsaturatedheterogeneous group has one double bond.

The term “hydrocarbon group” or “hydrocarbyl group” means a chain of 1to 25 carbon atoms, typically 1 to 12 carbon atoms, more typically 1 to10 carbon atoms, and most typically 1 to 8 carbon atoms. Hydrocarbongroups may have a linear or branched chain structure. Typicalhydrocarbon groups have one or two branches, typically one branch.Typically, hydrocarbon groups are saturated. Unsaturated hydrocarbongroups may have one or more double bonds, one or more triple bonds, orcombinations thereof. Typical unsaturated hydrocarbon groups have one ortwo double bonds or one triple bond; more typically unsaturatedhydrocarbon groups have one double bond.

When the term “unsaturated” is used in conjunction with any group, thegroup may be fully unsaturated or partially unsaturated. However, whenthe term “unsaturated” is used in conjunction with a specific groupdefined herein, the term maintains the limitations of that specificgroup. For example, an unsaturated “carbocyclic group”, based on thelimitations of the “carbocyclic group” as defined herein, does notencompass an aromatic group.

The terms “carboxy group” or “carboxyl group”, whether used alone orwith other terms, such as “carboxyalkyl group”, denotes —(C═O)—O— orC(O)O.

The term “carbonyl group”, whether used alone or with other terms, suchas “aminocarbonyl group”, denotes —(C═O)— or C(O) The terms“alkylcarbonyl group” denotes carbonyl groups which have beensubstituted with an alkyl group. In certain embodiments, “loweralkylcarbonyl group” has lower alkyl group as described above attachedto a carbonyl group.

The term “aminoalkyl group” encompasses linear or branched alkyl groupshaving one to about ten carbon atoms any one of which may be substitutedwith one or more amino groups. In some embodiments, the aminoalkylgroups are “lower aminoalkyl” groups having one to six carbon atoms andone or more amino groups. Examples of such groups include aminomethyl,aminoethyl, aminopropyl, aminobutyl and aminohexyl.

The term “alkylaminoalkyl group” encompasses aminoalkyl groups havingthe nitrogen atom independently substituted with an alkyl group. Incertain embodiments, the alkylaminoalkyl groups are“loweralkylaminoalkyl” groups having alkyl groups of one to six carbonatoms. In other embodiments, the lower alkylaminoalkyl groups have alkylgroups of one to three carbon atoms. Suitable alkylaminoalkyl groups maybe mono or dialkyl substituted, such as N-methylaminomethyl, N,N-dimethyl-aminoethyl, N, N-diethylaminomethyl and the like.

The term “aralkyl group” encompasses aryl-substituted alkyl groups. Inembodiments, the aralkyl groups are “lower aralkyl” groups having arylgroups attached to alkyl groups having one to six carbon atoms. In otherembodiments, the lower aralkyl groups phenyl is attached to alkylportions having one to three carbon atoms. Examples of such groupsinclude benzyl, diphenylmethyl and phenylethyl. The aryl in said aralkylmay be additionally substituted with halo, alkyl, alkoxy, haloalkyl andhaloalkoxy.

The term “arylalkenyl group” encompasses aryl-substituted alkenylgroups. In embodiments, the arylalkenyl groups are “lower arylalkenyl”groups having aryl groups attached to alkenyl groups having two to sixcarbon atoms. Examples of such groups include phenylethenyl. The aryl insaid arylalkenyl may be additionally substituted with halo, alkyl,alkoxy, haloalkyl and haloalkoxy.

The term “arylalkynyl group” encompasses aryl-substituted alkynylgroups. In embodiments, arylalkynyl groups are “lower arylalkynyl”groups having aryl groups attached to alkynyl groups having two to sixcarbon atoms. Examples of such groups include phenylethynyl. The aryl insaid aralkyl may be additionally substituted with halo, alkyl, alkoxy,haloalkyl and haloalkoxy. The terms benzyl and phenylmethyl areinterchangeable.

The term “alkylthio group” encompasses groups containing a linear orbranched alkyl group, of one to ten carbon atoms, attached to a divalentsulfur atom. In certain embodiments, the lower alkylthio groups have oneto three carbon atoms. An example of “alkylthio” is methylthio, (CH₃S—).

The term “alkylamino group” denotes amino groups which have beensubstituted with one alkyl group and with two alkyl groups, includingterms “N-alkylamino” and “N,N-dialkylamino”. In embodiments, alkylaminogroups are “lower alkylamino” groups having one or two alkyl groups ofone to six carbon atoms, attached to a nitrogen atom. In otherembodiments, lower alkylamino groups have one to three carbon atoms.Suitable “alkylamino” groups may be mono or dialkylamino such asN-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino and thelike.

The term “arylamino group” denotes amino groups which have beensubstituted with one or two aryl groups, such as N-phenylamino. The“arylamino” groups may be further substituted on the aryl ring portionof the group.

The term “heteroarylamino” denotes amino groups which have beensubstituted with one or two heteroaryl groups, such as N-thienylamino.The “heteroarylamino” groups may be further substituted on theheteroaryl ring portion of the group.

The term “aralkylamino group” denotes amino groups which have beensubstituted with one or two aralkyl groups. In other embodiments, thereare phenyl-C₁-C₃-alkylamino groups, such as N-benzylamino. The“aralkylamino” groups may be further substituted on the aryl ringportion of the group.

The term “alkylaminoalkylamino group” denotes alkylamino groups whichhave been substituted with one or two alkylamino groups. In embodiments,there are C₁-C₃-alkylamino-C₁-C₃-alkylamino groups.

The term “arylthio group” encompasses aryl groups of six to ten carbonatoms, attached to a divalent sulfur atom. An example of “arylthio” isphenylthio. The term “aralkylthio group” encompasses aralkyl groups asdescribed above, attached to a divalent sulfur atom. In certainembodiments there are phenyl-C₁-C₃-alkylthio groups. An example of“aralkylthio” is benzylthio.

The term “aryloxy group” encompasses optionally substituted aryl groups,as defined above, attached to an oxygen atom. Examples of such groupsinclude phenoxy.

The term “aralkoxy group” encompasses oxy-containing aralkyl groupsattached through an oxygen atom to other groups. In certain embodiments,aralkoxy groups are “lower aralkoxy” groups having optionallysubstituted phenyl groups attached to lower alkoxy group as describedabove.

The term “cycloalkyl group” includes saturated carbocyclic groups. Incertain embodiments, cycloalkyl groups include C₃-C₆ rings. Inembodiments, there are compounds that include, cyclopentyl, cyclopropyl,and cyclohexyl.

The term “cycloalkenyl group” includes carbocyclic groups that have oneor more carbon-carbon double bonds; conjugated or non-conjugated, or acombination thereof. “Cycloalkenyl” and “cycloalkyldienyl” compounds areincluded in the term “cycloalkenyl”. In certain embodiments,cycloalkenyl groups include C₃-C₆ rings. Examples include cyclopentenyl,cyclopentadienyl, cyclohexenyl and cycloheptadienyl. The “cycloalkenyl”group may have 1 to 3 substituents such as lower alkyl, hydroxyl, halo,haloalkyl, nitro, cyano, alkoxy, lower alkylamino, and the like.

The term “suitable substituent”, “substituent” or “substituted” used inconjunction with the groups described herein refers to a chemically andpharmaceutically acceptable group, i.e., a moiety that does not negatethe therapeutic activity of the inventive compounds. It is understoodthat substituents and substitution patterns on the compounds of theinvention may be selected by one of ordinary skill in the art to providecompounds that are chemically stable and that can be readily synthesizedby techniques known in the art, as well as those methods set forthbelow. If a substituent is itself substituted with more than one group,it is understood that these multiple groups may be on the samecarbon/member atom or on different carbons/member atoms, as long as astable structure results. Illustrative examples of some suitablesubstituents include, cycloalkyl, heterocyclyl, hydroxyalkyl, benzyl,carbonyl, halo, haloalkyl, perfluoroalkyl, perfluoroalkoxy, alkyl,alkenyl, alkynyl, hydroxy, oxo, mercapto, alkylthio, alkoxy, aryl orheteroaryl, aryloxy or heteroaryloxy, aralkyl or heteroaralkyl, aralkoxyor heteroaralkoxy, HO—(C═O)—, amido, amino, alkyl- and dialkylamino,cyano, nitro, carbamoyl, alkylcarbonyl, alkoxycarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, arylcarbonyl, aryloxycarbonyl,alkylsulfonyl, and arylsulfonyl. Typical substituents include aromaticgroups, substituted aromatic groups, hydrocarbon groups including alkylgroups such as methyl groups, substituted hydrocarbon groups such asbenzyl, and heterogeneous groups including alkoxy groups such as methoxygroups.

The term “fused” means in which two or more carbons/member atoms arecommon to two adjoining rings, e.g., the rings are “fused rings”.

Cross-linking agent(s) are provided. The cross-linking agent(s)described herein may be used for making composition(s) such as desiredpolymeric composition(s). In certain embodiments, the cross-linkingagent(s) can be used to make hydrogel material(s), which includes, andwithout being limited thereto, silicon hydrogel materials. Suchmaterials/compositions are useful in the manufacture of biocompatiblemedical devices, for example, having desirable physical properties foruse as contact lense(s) and/or stimulating device(s).

In embodiments, the cross-linking agent(s) described herein possessdual-reactivity.

In additional embodiments, hydrogel material(s) or silicon hydrogelmaterial(s) are prepared from at least one (meth)acrylate monomer, atleast one N-vinyl pyrolidone or its derivatives, and one or morecross-linking agent(s)(s). The cross-linking agent(s) described hereinpossess dual-reactivity. For example, the cross-linking agent(s) canprovide at least some crosslinks between the polymer chains thatessentially comprise units of (meth)acrylate monomer and the polymerchains that essentially comprise units of vinyl monomer and N-vinylpyrolidone units. This dual-reactive reactive approach allows a personof ordinary skill to tune the hydrogel matrix in which some hydrophilicvinyl polymer chains or acrylamide chains have a greater ability to moveor migrate within the hydrogel polymeric framework than otherhydrophilic vinyl polymer chains, particularly in a physiologicalaqueous environment. Without being bound by theory, the dual-reactiveapproach of the cross-linking agent(s)(s) is believed to anchor somehydrophilic vinyl polymer chains and acrylamide chains to the(meth)acrylate polymer chain more strongly than others to create adimensionally stable, hydrogel polymer framework, and other vinylpolymer chains have relatively greater mobility within the sameframework. Moreover, these anchored vinyl chains can be further anchoredto the hydrogel framework through additional crosslinks within the(meth)acrylate framework. It is this type of molecular anchoring ofhydrophilic vinyl polymer that may explain, in embodiments, the observedsurface enhancement (wettability and/or lubricity) along with optimalphysical properties such as modulus of elasticity, oxygen permeability,and a low level of extractables during manufacture—all of which,collectively, must be considered and balanced for a contact lens that aconsumer demands in terms of its comfort over at least 18 hours (in thecase of a daily replacement lens), or over two to four weeks (in thecase of an extended wear lens). The term, physiological aqueousenvironment, means an aqueous borate-buffered saline (BBS) solution witha pH of 7.4-7.5, a compositional solution well known to a person ofordinary skill in the art of hydrogel materials for medical devices.

In embodiments, matching the reactivity of each monomer in the polymercomposition using the cross-linking agent(s) described herein mayprovide for a relatively consistent hydrogel polymer framework, which isa commercial consideration in that the hydrogel material can bereproduced within production specifications for a given polymerizationmonomer mix. Such consistency is useful when it comes to the dimensionalstability of the hydrogel matrix over time, e.g., in typicalembodiments, a contact lens should maintain dimensional stability in itspackaging for at least three years or more as well as maintaindimensional stability when positioned in the eye. Priorcopolymerizations of at least one (meth)acrylate monomer with at leastone vinyl monomer and a conventional cross-linking agent(s) do notconsistently exhibit this level of dimensional stability.

In other embodiments, the cross-linking agent(s) are designed fordual-phase polymerization as they are designed with dual reactive sitesin one agent to polymerize and incorporate both the (meth)acrylate(fast) and vinyl (slow), i.e., monomers of two different free-radicalpolymerization rates, into a hydrogel polymer framework or network. Inthe absence of such a cross-linking agent(s), the formedinterpenetrating poly(NVP) is too mobile within the hydrogel framework,and as the hydrogel swells in a physiological aqueous environment, thepoly(NVP) is released from the framework. Moreover, in the absence of adual-reactive cross-linking agent(s), the resulting hydrogel may releasea high level of extractables, e.g., low molecular weight poly(NVP) andoligomers, and one often observes a material with poor dimensionalstability.

The cross-linking agent(s) may also provide a unique morphology usingthe dual phase polymerization where specific bioinspired functionalmonomers, for example, can be incorporated within the hydrogel polymerframework. Persons of skill in the art of making hydrogel materialsgenerally agree that the dual phase polymerizing results in two separatephases—a methacrylate-based phase and a PVP phase. By polymerizing, forexample, a fast polymerizing methacrylate phosphatidylcholine (MPC) anda slow polymerizing vinyl phosphatidylcholine carbonate (VPC), each ofthe two phases can be enriched with the bioinspired polymers. The slowpolymerizing VPC is expected to enrich the lens surface (because of itshigh mobility) and render a highly biocompatible VPC surface. The fastpolymerizing MPC is expected to encase the silicone component with ahighly hydrophilic polymer, and enhance the wetting and lubricity of thehydrogel surface because even with a dual-phase polymerization someamount of silicone component will be at or near the surface. Theresulting hydrogels materials can possess desirable physicalcharacteristics useful for contact lens materials including a lowmodulus of elasticity, oxygen permeability, suitable tear strength, alow level of extractables, and inherent wettability or lubricity.

In an embodiment, there is provided a compound of formula I:

-   -   R¹-R¹¹ are the same or different, and are each independently        selected from H, halo, hydroxyl, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, a substituted or unsubstituted        heteroaromatic group, or NR^(a)R^(b), wherein R^(a) and R^(b)        are the same or different, and are independently selected from        H, halo, hydroxyl, amino, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, or a substituted or        unsubstituted heteroaromatic group;    -   X¹ and X² are the same or different, and are each independently        selected from a direct bond, a heteroatom, C(O), a substituted        or unsubstituted hydrocarbon group, a substituted or        unsubstituted heterogeneous group, a substituted or        unsubstituted carbocyclic group, a substituted or unsubstituted        heterocyclic group, a substituted or unsubstituted aromatic        group, a substituted or unsubstituted heteroaromatic group, or        NR^(a); and    -   Z is selected from a heteroatom, C(O), a substituted or        unsubstituted hydrocarbon group, a substituted or unsubstituted        heterogeneous group, a substituted or unsubstituted carbocyclic        group, a substituted or unsubstituted heterocyclic group, a        substituted or unsubstituted aromatic group, a substituted or        unsubstituted heteroaromatic group, NR^(a), or        [SiR¹²R¹³O]_(w)SiR¹²R¹³, wherein R¹² and R¹³ are the same or        different, and are independently selected from H, halo,        hydroxyl, amino, a substituted or unsubstituted hydrocarbon        group, a substituted or unsubstituted heterogeneous group, a        substituted or unsubstituted carbocyclic group, a substituted or        unsubstituted heterocyclic group, a substituted or unsubstituted        aromatic group, or a substituted or unsubstituted heteroaromatic        group, and w is from 0 to 60.

In another embodiment, there is provided a compound of formula I1:

-   -   R¹-R¹¹ are the same or different, and are each independently        selected from H, halo, hydroxyl, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, a substituted or unsubstituted        heteroaromatic group, or NR^(a)R^(b), wherein R^(a) and R^(b)        are the same or different, and are independently selected from        H, halo, hydroxyl, amino, a substituted or unsubstituted        hydrocarbon group, a substituted or unsubstituted heterogeneous        group, a substituted or unsubstituted carbocyclic group, a        substituted or unsubstituted heterocyclic group, a substituted        or unsubstituted aromatic group, or a substituted or        unsubstituted heteroaromatic group;    -   X¹ and X² are the same or different, and are each independently        selected from a direct bond, a heteroatom, C(O), a substituted        or unsubstituted hydrocarbon group, a substituted or        unsubstituted heterogeneous group, a substituted or        unsubstituted carbocyclic group, a substituted or unsubstituted        heterocyclic group, a substituted or unsubstituted aromatic        group, a substituted or unsubstituted heteroaromatic group, or        NR^(a); and    -   Z is selected from a heteroatom, C(O), a substituted or        unsubstituted hydrocarbon group, a substituted or unsubstituted        heterogeneous group, a substituted or unsubstituted carbocyclic        group, a substituted or unsubstituted heterocyclic group, a        substituted or unsubstituted aromatic group, a substituted or        unsubstituted heteroaromatic group, NR^(a), or        [SiR¹²R¹³O]_(w)SiR¹²R¹³, wherein R¹² and R are the same or        different, and are independently selected from H, halo,        hydroxyl, amino, a substituted or unsubstituted hydrocarbon        group, a substituted or unsubstituted heterogeneous group, a        substituted or unsubstituted carbocyclic group, a substituted or        unsubstituted heterocyclic group, a substituted or unsubstituted        aromatic group, or a substituted or unsubstituted heteroaromatic        group, and w is from 0 to 60.

In accordance with further embodiments, R¹-R¹¹ are the same ordifferent, and are each independently selected from H, halo, hydroxyl, asubstituted or unsubstituted hydrocarbon group, or a substituted orunsubstituted heterogeneous group. In other embodiments, R¹-R¹¹ are thesame or different, and are each independently selected from H, halo,hydroxyl, a substituted or unsubstituted C₁-C₆ alkyl, a substituted orunsubstituted C₁-C₆ alkoxy, or a substituted or unsubstituted C₁-C₆alkanol. In still other embodiments, R¹-R¹¹ are the same or different,and are each independently selected from H or a substituted orunsubstituted hydrocarbon group. In further embodiments, R¹-R¹¹ are thesame or different, and are each independently selected from H or asubstituted or unsubstituted alkyl group. In another embodiment, R¹-R¹¹are the same or different, and are each independently selected from H ora substituted or unsubstituted C₁-C₆ alkyl. In yet another embodiment,R¹-R¹¹ are the same or different, and are each independently selectedfrom H or unsubstituted C₁-C₆ alkyl. In another embodiment, R¹-R¹¹ arethe same or different, and are each independently selected from H ormethyl. In still other embodiments, R¹, R², R¹⁰, and R¹¹ are H.

In further embodiments, X¹ and X² are the same or different, and areeach independently selected from a direct bond, O, NR^(a), C(O),C(O)NR^(a), NR^(a)C(O), OC(O)NR^(a), NR^(a)C(O)O, NR^(a)C(O)NH,NHC(O)NR^(a), C(O)O, OC(O), NHC(O)NHZ₀—NH—C(O)NH, OC(O)NHZ₀—NH—C(O)O,OC(O)NHZ₀—NH—C(O)NH, or NHC(O)NHZ₀—NH—C(O)O; where Z₀ is a linear orbranched C₂-C₁₂ alkylene divalent radical, or a C₅-C₇ cycloaliphaticdivalent radical, each of which can optionally include one or morelinkages of O, NR^(a) and C(O). In another embodiment, X¹ and X² are thesame or different, and are each independently selected from a directbond, O, NR^(a), C(O), C(O)NR^(a), NR^(a)C(O), NR^(a)C(O), OC(O)NR^(a),NR^(a)C(O)O, C(O)O, or OC(O). In another embodiment, R^(a) is selectedfrom H or a substituted or unsubstituted hydrocarbon group. In a furtherembodiment, R^(a) is selected from H or unsubstituted C₁-C₆ alkyl. In anadditional embodiment, R^(a) is selected from H or methyl. In otherembodiments, X¹ and X² are the same or different, and are eachindependently selected from a direct bond, O, or NR^(a).

In other embodiments, Z is selected from a direct bond, a substituted orunsubstituted hydrocarbon group, a substituted or unsubstitutedheterogeneous group, or [SiR¹²R¹³O]_(w)SiR¹²R¹³. In another embodiment,Z is selected from a direct bond, a substituted or unsubstitutedhydrocarbon group, a substituted or unsubstituted heterogeneous group,or [SiR¹²R¹³O]_(w)SiR¹²R¹³, wherein R¹² and R¹³ are the same ordifferent, and are independently selected from C₁-C₄ alkyl or phenyl,and w is from 0 to 60. In yet other embodiments, Z is selected from adirect bond, or a substituted or unsubstituted hydrocarbon group. Inother embodiments, Z is selected from a substituted or unsubstitutedhydrocarbon group. In certain embodiments, Z is selected from asubstituted or unsubstituted alkyl group. In embodiments, Z is selectedfrom a substituted or unsubstituted C₁-C₂₀ alkyl. In other embodiments,Z is selected from a substituted or unsubstituted C₁-C₆ alkyl. Infurther embodiments, Z is selected from an unsubstituted C₁-C₆ alkyl. Inanother embodiment, Z is selected from a substituted or unsubstitutedaromatic group. In yet other embodiments, Z is selected from asubstituted or unsubstituted phenyl group. In other embodiments, Z isselected from a C₁-C₁₂ unsubstituted or substituted, linear or branchedalkylene divalent radical, where each alkylene divalent radical canoptionally include one or more linkages of O, NR^(a), and C(O), anunsubstituted phenylene divalent radical, a C₅-C₇ cycloaliphaticdivalent radical, or a C₇-C₁₂ arylalkylene divalent radical.

In another embodiment, the compound is Formula III

In a further embodiment, the compound is selected from one or more of

In certain embodiments, the compound is selected from one of thecompounds defined above.

In certain embodiments, there is provided a composition comprising oneor more of the compounds defined above.

In certain embodiments, the composition comprises one of the compoundsdefined above.

In further embodiments, the use of one or more of the compoundsdescribed above as cross-linking agent(s).

In certain embodiments, the use of one of the compounds described aboveas cross-linking agent(s).

In other embodiments, the use of one or more of the compounds describedabove to produce biocompatible medical devices(s).

In certain embodiments, the use of one of the compounds described aboveto produce biocompatible medical devices(s).

In further embodiments, there is provided a method of producingbiocompatible medical devices(s), the method comprising reacting atleast one of the compounds described above with at least one monomer.

In other embodiments, there is provides a composition comprising atleast one (meth)acrylic monomer, at least one vinyl containing monomerand at least one of the compounds described above. The at least one ofthe compounds acting as cross-linking agent(s), which include at leastone free-radical reactive site for vinyl-containing monomer and at leastone free-radical reactive site for meth(acrylic)-containing monomer.Following polymerization by thermal or photochemical initiation, thecompositions can provide a hydrogel material with a wettable surface,and in many instances, a surface that is enriched with the slowreacting, poly(cyclic lactam) copolymer component.

Although the above described dual-reactive cross-linking agent(s) andthe dual-phase polymerization can be used with many polymeric systems,in particular embodiments, the dual-phase polymerization can be usedwith hydrogel materials, such as, and without be limiting thereto, bothconventional and silicone hydrogels. In addition, the polymercompositions may provide an opportunity to design and plan for an uniquemorphology using the dual phase polymerization where bioinspiredmonomers of dual reactivity are simultaneous incorporated with thepolymeric network. These hydrogels compositions may possess desirablephysical characteristics useful for contact lens materials. Suchproperties include, for example, low modulus of elasticity, a high levelof oxygen permeability, suitable tear strength, a low level ofextractables, and inherent wettability or lubricity.

The composition can also include a cross-linking agent(s) that is usedto crosslink primarily with the (meth)acrylate monomer in thecomposition. At times, this second cross-linking agent(s) is referred toherein as a (meth)acrylate cross-linking agent(s). Accordingly, atypical composition may include a dual-reactive cross-linking agent(s)of formulae I, II, or III and a (meth)acrylate cross-linking agent(s).

In embodiments, the cross-linking agent(s) of formulae I, II, or III ispresent in the composition from 0.02% to 5.0% by weight, from about0.05% to about 2.0% by weight, or from 0.08% to 0.8% by weight, based onthe weight of the total composition excluding the weight of any diluentpresent in the composition. In fact, all stated percent by weight of anyrespective component in the described compositions is based on the totalweight of the composition excluding the weight of any diluent present inthe composition.

In certain embodiments, the compositions include a (meth)acrylatecross-linking agent(s) to provide additional structural stability to thehydrogel polymer framework. Many of these (meth)acrylate cross-linkingagent(s) are known in the art of hydrogel materials. The (meth)acrylatecross-linking agent(s) include, but are not limited to, any onedifunctional or multifunctional cross-linking agents, and anycombination thereof. Representative examples of such cross-linkingagents include, but are not limited to, tripropylene glyceroldiacrylate, ethylene glycol dimethacrylate, tetraethylene glycoldimethacrylate, poly(ethylene glycol diacrylate) (PEG400 or PEG600),allyl methacrylate and the like. In addition, diacrylates anddimethacrylates of triethylene glycol, butylene glycol, neopentylglycol, ethylene glycol, hexane-1,6-diol and thio-diethylene glycol;trimethylolpropane triacrylate, N,N′-dihydroxyethylene bisacrylamide,diallyl phthalate, triallyl cyanurate, divinylbenzene, ethylene glycoldivinyl ether, or N,N′-methylene-bis-(meth)acrylamide, sulfonateddivinylbenzene, divinylsulfone.

If present, the (meth)acrylate cross-linking agent(s) can be used in aneffective amount to balance the requirement of a structural hydrogelframework with the water content or the inherent wettability of theresulting hydrogel material. The (meth)acrylate cross link agent can bepresent in the composition from 0.1% to 3% by weight, from about 0.2% toabout 1% by weight, or from 0.2% to 0.6% by weight.

In general embodiments, to achieve a hydrogel material that includes aproper balance of desired properties, particularly, if the hydrogelmaterial is to be a material for a contact lens, the need for a stablehydrogel polymer framework must be balanced with the wettability andlubricity of the hydrogel surface in a physiological aqueousenvironment. Accordingly, the amount of (meth)acrylate cross link agentmay exceed the amount of cross-linking agent(s) of formulae I, II, orIII and a hydrogel material with the desired balance of properties canbe formed. Accordingly, in one compositional embodiment, the(meth)acrylate cross-linking agent(s) is present in an amount thatexceeds the amount of cross link agent of formulae I, II, or III by atleast 2×, typically at least 3×, up to about 10×, in terms of percent byweight in the composition. Alternatively, in terms of a weight ratio of(meth)acrylate cross link agent to cross-linking agent(s) of formulae I,II, or III, the weight ratio is from 2:1 to 10:1, typically from 2:1 to6:1.

The described dual-reactive cross-linking agent(s) are particularlydesigned for hydrogel formulations that include at least one N-vinyllactam monomer as the at least one vinyl monomer. Illustrative examplesof N-vinyl lactams that are present in the hydrogel formulations,include but not limited to, N-vinyl-2-pyrrolidinone (NVP), N-(1-methylvinyl) pyrrolidinone, N-vinyl-2-piperidone and N-vinyl-2-caprolactam,each of which can be substituted in the lactam ring by one or more loweralkyl groups such as methyl, ethyl or propyl, e.g., N-vinyl-5-methylpyrrolidinone, N-vinyl-3,3-dimethyl pyrrolidinone, N-vinyl-5-ethylpyrrolidinone and N-vinyl-6-methyl piperidone. A typical monomer isN-vinyl-2-pyrrolidinone. Any one of the above N-vinyl lactams can beused alone or in admixture with other lactam monomers to providehydrogel materials with the properties of interest. Illustrative of theother lactam monomers are, for example, N-vinyl imidazole, N-vinylsuccinimide, N-vinyl diglycolylimide, N-vinyl glutarimide,N-vinyl-3-morpholinone and N-vinyl-5-methyl-3-morpholinone.

In a typical hydrogel material, the N-vinyl lactam monomer(s) can beused in conjunction with one or more hydrophobic and/or hydrophilicco-monomers. If used in conjunction with a co-monomer, the N-vinyllactam will constitute at least 60% of the copolymer and more typicallyfrom 70% to 90% by weight of the total monomers present in the monomerformulation.

Furthermore, the ratio of hydrophobic co-monomer to hydrophilicco-monomer present in a monomer formulation in preparing the N-vinyllactam, can be varied as desired to obtain the particular combination ofpolymer properties desired for the particular application. The typicalamount of N-vinyl lactam in the polymer composition is about 70 to about90 percent by weight to achieve a relatively high water content of about70% to about 90% by weight.

Water content is measured by individually placing the lens on a piece ofpremoistened Whatman #1 filter paper. The surface moisture is removed bylightly smoothing a second piece of premoistened Whatman #1 filter paperover the lens. After checking the accuracy of the balance with two knownweights, the lens is placed in a tared weigh boat. The wet weight isrecorded to the nearest 0.1 mg and the lens transferred to the lensholder, concave side up (this allows the lens identity to be maintainedto match wet and dry weights). After the lens holders are full, they areplaced on a spindle with a plastic spacer between them and placed in aglass jar approximately ½ full of desiccant. The jar is capped and thelid tightened, then loosened slightly to prevent pressure buildup. Thejar with lenses is placed in a 500-650 watt microwave oven along with a400 ml beaker containing at least 200 ml of distilled water with boilingbeads to keep the jar from becoming overheated. The jar is microwaved at500-650 watts for 10 minutes; the start time and date are recorded onthe paperwork. When the cycle finishes, the jar is removed from themicrowave and allowed to cool on the bench for 30 minutes; time out anddate are also recorded. When cool, the lenses are individually weighedand their dry weights recorded to the nearest 0.1 mg, matching the dryweights to the corresponding wet weight. The water content is expressedas % water according to the following formula: Water Content is [(wetweight−dry weight)/wet weight]×100.

(Meth)acrylate monomers polymerize very rapidly while the at least onevinyl monomer, polymerizes relatively slowly and fail to effectivelycopolymerize resulting in a high level of uncrosslinked poly(NVP), thelatter of which can be released from the hydrogel resulting in a loss ofdimensional stability and a loss of surface wettability. Thedual-reactive cross-linking agent(s) described herein can allow one tocontrol the amount of cross-linking of the formed poly(NVP) with thehydrogel network, and in particular the cross linking with the(meth)acrylate polymers of the network. The control of crosslink densitycan affect the wettability, lubricity, tear strength, extractables anddimensional stability of the resulting hydrogel material. Due to thedual-reactive sites of the described cross-linking agent(s), the agentscan form a crosslink between the essentially (meth)acrylate homopolymerand the essentially vinyl homopolymer resulting in hydrogel materialsthat possess low extractables and excellent dimensional stability.

A hydrogel contact lens prepared with at least 70% by weight of N-vinyllactam monomer, and a cross-linking agent(s) of formulae I, II, or III,may possess a tear strength of at least about 0.06 N/mm, at least about0.07 N/mm, or at least about 0.08 N/mm. The hydrogel contact lens mayalso possess a water content of at least about 40% by weight, at leastabout 45% by weight, at least about 50% by weight, at least about 65% byweight, at least about 70% by weight, at least about 71% by weight, atleast about 77% by weight, or at least about 80% by weight. The hydrogelcontact lens may also possess a modulus of elasticity of at least about0.30 MPa, at least about 0.35 MPa, at least about 0.40 MPa, or at leastabout 0.45 MPa.

A typical hydrogel contact lens can possess the following mechanicalproperties: a tear strength of at least about 0.06 N/mm; a water contentof at least about 45% by weight; and a modulus of elasticity of at leastabout 0.30 MPa.

Another typical hydrogel contact lens can possess the followingmechanical properties: a tear strength of at least about 0.07 N/mm; awater content of at least about 50% by weight; and a modulus ofelasticity of at least about 0.40 MPa.

Another typical hydrogel contact lens can possess the followingmechanical properties: a tear strength of at least about 0.08 N/mm; awater content of at least about 65% by weight; and a modulus ofelasticity of at least about 0.45 MPa.

The resulting hydrogel materials may possess a highly wettable hydrogel“surface” enriched with the slow reacting monomer/polymer component. Thedual reactivity approach can also allow for the surface enrichment, orexposure, of chemical functionality capable of providing for improvedclinical performance. This functionality can be bioinspired in nature.For example, the addition of a monomer with vinyl carbonate phosphatidylcholine, which copolymerizes well with NVP, will result in aphosphatidyl choline enriched lens surface. Hydrogel materials with thissurface functionality may exhibit such characteristics as a low affinityfor proteins, lipids, and bacteria. In addition, the use of bioinspiredfast reacting methacrylate based monomer combined with a silicone basedmonomer can provide for improved wetting and compatibility with the PVPreacting phase.

The chemistry of hydrogels is well known and there exists a variety ofmonomers that can be used to make the hydrogel materials. In particular,monomers of interest to the contact lens art include, for example,acrylate, acrylamide, methacrylate, methacrylamide, styrene-containingmonomers, dimethacrylate and dimethacrylamide monomers, vinylamide-containing monomers, vinyl carbonate/carbamate/urea monomers, and(meth)acrylate/(meth) acrylamide-capped prepolymers. All of theabove-mentioned monomers and prepolymers may further includepolysiloxanes and polyfluorosiloxanes, such as ethylenically terminatedmethacrylate capped urethane-containing polysiloxane prepolymers,fluorine containing polysiloxanes, polyether containing siloxanes, andpolysiloxanes monomers, such as, α,ω-bis(methacryloxybutyl) polysiloxane(M₂ D₂₅).

Suitable monomers may be represented by the general formulae:

-   -   wherein X is O or NR^(c), where R^(c) is hydrogen, C₁-C₄ alkyl        or C₁-C₃ alkanol; R1 is H or CH₃; and R2 and R3 are        independently hydrogen, a C₁-C₁ alkyl, C₃-C₁₈ cycloalkyl, C₃-C₁₈        cycloalkylalkyl, C₃-C₁₈ cycloalkenyl, C₅-C₃₀ aryl, C₅-C₃₀        arylalkyl, C₁-C₁₈ alkyl siloxysilane or C₁-C₁ alkyl siloxane,        each of which can be optionally substituted, linear or branched,        or R2 and R3 together with the nitrogen atom to which they are        bonded are joined together to form a heterocyclic group.

The vinyl monomers of particular interest in hydrogel systems are vinylhydrophilic monomers, and in particular, a class of N-vinyl hydrophilicmonomer. For example, the vinyl hydrophilic monomer is selected from anN-vinylamide monomer of formula A, a vinyl pyrrolidone of formula B, Cor D, or an n-vinyl piperidone of formula E:

wherein

-   -   R^(t) is H or CH₃, and in one embodiment R^(t) is H;    -   R^(s) and R^(w) are independently selected from H, CH₃, CH₂CH₃,        CH₂CH₂CH₃, C(CH₃)₃;    -   R^(u) is selected from H, CH₃, CH₂CH₃; and    -   R^(v) is selected from CH₂, CHCH₃ and C(CH₃)₂;    -   R^(x) is selected from CH═CH₂, CCH₃═CH₂, and CH═CHCH₃.

In one embodiment, the hydrophilic vinyl monomer is selected fromethylene glycol vinyl ether (EGVE), di(ethylene glycol) vinyl ether(DEGVE), and the N-vinyl monomer includes, but not limited to, N-vinyllactams, including N-vinyl pyrrolidone (NVP),1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone,N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,1-n-propyl-3-methylene-2-pyrrolidone,1-n-propyl-5-methylene-2-pyrrolidone,1-isopropyl-3-methylene-2-pyrrolidone,1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-methyl acetamide (VMA),N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide,N-vinyl acetamide, N-vinyl isopropylamide, allyl alcohol, N-vinylcaprolactam, N-2-hydroxyethyl vinyl carbamate, N-carboxyvinyl-β-alanine(VINAL), N-carboxyvinyl-α-alanine or combinations thereof.

In another embodiment the slow-reacting hydrophilic monomer is selectedfrom NVP, VMA and 1-methyl-5-methylene-2-pyrrolidone, N-vinylpiperidone, N-vinyl-e-caprolactam, N-vinylimidazolidone,N-vinylsuccinimide, N-vinylformamide and N-vinyl urea, N-vinylcarbamate,or combinations thereof. Another vinyl monomer of interest is an O-vinylcarbonate and N-vinyl carbamate that includes zwitterionic functionalitysuch as carboxy betaine and phosphatidyl choline, and mixtures thereof.Because hydrogel materials rich in poly(NVP) have relatively high watercontent many compositions may include N-vinyl-2-pyrrolidone (NVP), inrelatively high concentration, e.g., from 50% to 90% by weight, based onthe weight of the total composition excluding the weight of any diluentpresent in the composition.

The compositions can also include other hydrophilic monomers that arewell known in the contact lens art, and include, but not limited to,2-hydroxyethyl methacrylate (HEMA), glyceryl monomethacrylate (GM) and2-acrylamido-2-methyl propane sulfonic acid (AMPS). Examples of otherhydrophilic monomers useful for polymerization with the vinyl monomerinclude, but are not limited to, unsaturated carboxylic acids, e.g.,acrylic acids, methacrylic acids and the like; (meth)acrylic substitutedalcohols, e.g., 3-hydroxypropyl methacrylate, 3-hydroxypropyl acrylateand the like, or combinations thereof. Still other hydrophilic monomersinclude the azetidinium and the oxazolone-based monomers disclosed inU.S. Pat. No. 4,910,277.

As noted, the additional hydrophilic monomer may be typically(meth)acrylate monomer, and therefore, will typically copolymerize withother (meth)acrylate monomer in the composition with a similarfree-radical rate of reactivity. Hydrophilic monomer with hydroxylfunctionality is of interest because the hydroxyl functionality canprovide additional surface wettability of the resulting hydrogelmaterial. A particular monomer of interest is 2-hydroxyl ethylmethacrylate, which can be present in the composition from 5% to 30% byweight. In a typical composition, the N-vinyl-2-pyrrolidone is presentfrom 30% to 90% by weight, and the 2-hydroxyl ethyl methacrylate ispresent from 0.5% to 30% by weight.

In the absence of any one silicone-containing monomer, the hydrogelsformed are referred to in the art as conventional hydrogels. However,silicone hydrogels is another class of hydrogel materials of importancein the field of medical devices. Accordingly, one or moresilicone-containing monomers can be included in a composition ofinterest. Some well-known silicone-containing monomers include theTRIS-like and trisiloxane (siloxy silane) monomers represented by thefollowing structures.

-   -   wherein h is 1 to 18 and each R³ independently denotes a lower        alkyl radical, or phenyl radical. Representative examples of        such acrylate ester and/or methacrylate ester-containing        monomers include        3-methacryloyloxypropyltris(trimethylsiloxy)silane or        (3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane),        sometimes referred to as TRIS and SIGMA, respectively, and are        commercially available from such sources as Gelest, Inc.        (Morrisville, PA). Other examples of siloxy silanes include,        pentamethyldisiloxanyl methylmethacrylate,        phenyltetramethyl-disiloxanylethyl acrylate,        methyldi(trimethylsiloxy) methacryloxymethyl silane,        3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate,        3[tris(trimethylsiloxy)silyl]propyol allyl carbamate,        3-tris(trimethylsiloxy)silyl] propyl vinyl carbonate, or        combinations thereof. Additional examples of typical siloxy        silanes include        N-[tris(trimethylsiloxy)silylpropyl]-methacrylamide,        N-[tris(dimethylpropyl-siloxy)silylpropyl] methacrylamide,        N-[tris(dimethylphenylsiloxy)-silyl propy](meth)acrylamide,        N-[tris(dimethylethylsiloxy)silylpropyl](meth)acrylamide,        N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)-2-methyl        acrylamide,        N-(2-hydroxy-3-(3-(bis(trimethyl-silyloxy)methylsilyl)propyloxy)propyl)        acrylamide, N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)        methylsilyl)propyloxy) propyl]-2-methyl acrylamide,        N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)        methylsilyl)propyloxy)propyl]acrylamide,        N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)        silyl)-propyloxy)propyl)-2-methyl acrylamide,        N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)-propyl)acrylamide,        N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methyl        acrylamide,        N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide,        N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl        acrylamide,        N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide,        N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)-propyloxy)propyl]-2-methyl        acrylamide,        N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)-propyl]acrylamide,        3-methacryloxy propylpentamethyl disiloxane,        3-methacryloxy-2-(2-hydroxy        ethoxy)-propyloxy)propylbis(trimethylsiloxy) methylsilane,        N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)        silyl carbamate, 3-(trimethylsilyl)-propylvinyl carbonate,        3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane,        3-[tris(trimethylsiloxy)silyl]propylvinyl carbamate,        3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate,        3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate,        t-butydimethyl-siloxyethyl vinyl carbonate, trimethylsilylethyl        vinyl carbonate, trimethylsilylmethyl vinyl carbonate, or        combinations thereof.

Silicone monomers referred in the art as silicone monofunctional monomercan also be included in the described compostions. See, U.S. Pat. No.8,937,110 to Vanderlaan. Examples of some silicone monofunctionalmonomer include monomethacryloxyalkyl-polydimethylsiloxane methacrylatesselected from monomethacryloxypropyl terminated mono-n-butyl terminatedpolydimethylsiloxane, monomethacryloxypropyl terminated mono-n-methylterminated polydimethylsiloxane, monomethacryloxypropyl terminatedmono-n-butyl terminated polydiethylsiloxane, monomethacryloxypropylterminated mono-n-methyl terminated polydiethylsiloxane,N-(2,3-dihydroxypropane)-N′-(propyltetra(dimethylsiloxy)dimethylbutylsilane) acrylamide,α-(2-hydroxy-1-methacryloxypropyloxypropyl)-o-butyl-decamethyl-pentasiloxane,or combinations thereof.

In another embodiment, the silicone monofunctional monomer is selectedfrom monomethacryloxypropyl terminated mono-n-butyl terminatedpolydimethylsiloxane, monomethacryloxypropyl terminated mono-n-methylterminated polydimethylsiloxane, N-(2,3-dihydroxypropane)-N′-(propyltetra(dimethylsiloxy)dimethylbutylsilane)acrylamide,α-(2-hydroxy-1-methacryloxypropyloxypropyl)-o-butyl-decamethyl-pentasiloxane,or combinations thereof.

In another embodiment the silicone monofunctional monomer is selectedfrom acrylamide silicones general formulae (s1) through (s6) below.

The at least one silicone-containing monomer is present in the describedcompositions in an amount sufficient to provide the desired oxygenpermeability. In certain embodiments, oxygen permeabilities can begreater than about 60 barrers, greater than about 80 barrer, or in someother embodiments greater than about 90 barrer. Suitable amounts willdepend on the length of the siloxane chain included in thesilicone-containing monomers, with silicone-containing monomers havinglonger chains requiring less monomer. Amounts include from about 20% toabout 60% by weight, and in some embodiments from about 30% to about 55%by weight.

In certain silicone hydrogel compositions, one or more of thesilicone-containing monomer above are present in a composition fromabout 25% to about 80% by weight, or from about 20% to about 80% byweight. In a typical composition, the N-vinyl-2-pyrrolidone is presentfrom about 50% to about 90% by weight, 2-hydroxyl ethyl methacrylate ispresent from about 0.5% to about 25% by weight, and thesilicone-containing monomer is present from about 30% to about 70% byweight.

Specific bioinspired monomers include, but not limited to,carboxybetaines, sulfobetains and phosphobetaines, such as methacryloxyphosphatidyl choline (MPC), N-vinylcarboxy ethyl phosphatidyl choline,O-vinyl ethyl phosphatidyl choline carbonate,1-(3-sulfopropyl)-2-vinylpyridinium betaine,3-dimethyl(acryloyloxyethyl) ammonium propyl sulfonate, functionalsugars and proteins, or any one mixture of bioinspired monomer. Othersuitable bioinspired hydrophilic monomers will be apparent to oneskilled in the art. The bioinspired monomer is present from about 0.5%to about 16% by weight or from about 2% to about 6% by weight.

Useful hydrophobic monomers for use herein include, but are not limitedto, alkyl acrylates and methacrylates, 4-t-butyl-2-hydroxy cyclohexylmethacrylate (TBE), tert-butyl cyclohexyl methacrylate,isopropylcyclopentyl acrylate, tert-butylcyclohexyl acrylate, isobornylmethacrylate and the like; 2-ethylhexyl methacrylate, 2-phenyloxyethylmethacrylate, partially fluorinated acrylates, partially fluorinatedmethacrylates and the like, or combinations thereof.

In general, the copolymerization reaction can be conducted neat or witha suitable cosolvent. The monomeric mixture and optional cross linkingagent(s) are combined in the desired ratio, and then exposed to, forexample, ultraviolet (UV) light or electron beams in the presence of oneor more photoinitiator(s) or at a suitable temperature, for a timeperiod sufficient to form the copolymer. Heat may also be employed toinitiate the polymerization in which case a series of Vazo, peroxide orperoxy initiators, well-known in the art, may be used. Suitable reactiontimes will ordinarily range from about 1 minute to about 24 hours andtypically from about 1 hour to about 10 hours.

The use of UV or visible light in combination with photoinitiators iswell known in the art and is particularly suitable for formation of thecopolymer. Numerous photoinitiators of the type in question here arecommercial products. Photo initiators enhance the rapidity of the curingprocess when the photo curable compositions as a whole are exposed to,for example, ultraviolet radiation. Suitable photo initiators which areuseful for polymerizing the polymerizable mixture of monomers can becommercially available photo initiators. They are generally compoundswhich are capable of initiating the radical reaction of olefinicallyunsaturated double bonds on exposure to light with a wavelength of, forexample, about 260 to about 480 nm.

Examples of suitable photoinitiators for use herein include, but are notlimited to, one or more photoinitiators commercially available under the“IRGACURE”, “DAROCUR” and “SPEEDCURE” trade names (manufactures by CibaSpecialty Chemicals, also obtainable under a different name from BASF,Fratelli Lamberti and Kawaguchi), e.g., “IRGACURE” 184(1-hydroxycyclohexyl phenyl ketone), 907(2-methyl-1-[4-(methylthio)phenyl]-2-morpholino propan-1-one), 369(2-benzyl-2-N,N-dimethylamino-1-(4-morpholinophenyl)-1-butanone), 500(the combination of 1-hydroxy cyclohexyl phenyl ketone andbenzophenone), 651 (2,2-dimethoxy-2-phenyl acetophenone), 1700 (thecombination of bis(2,6-dimethoxybenzoyl-2,4,4-trimethyl pentyl)phosphineoxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one), and 819[bis(2,4,6-trimethyl benzoyl)phenyl phosphine oxide] and “DAROCUR” 1173(2-hydroxy-2-methyl-1-phenyl-1-propan-1-one) and 4265 (the combinationof 2,4,6-trimethylbenzoyldiphenyl-phosphine oxide and2-hydroxy-2-methyl-1-phenyl-propan-1-one); and the like and mixturesthereof. Other suitable photo initiators for use herein include, but arenot limited to, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO)and ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L), alkylpyruvates such as methyl, ethyl, propyl, and butyl pyruvates, and arylpyruvates such as phenyl, benzyl, and appropriately substitutedderivatives thereof. Generally, the amount of photo initiator can rangefrom about 0.05% w/w to about 5% w/w and typically from about 0.1% w/wto about 1% w/w.

Examples of suitable thermal initiators for use herein include, but arenot limited to, include the azo and peroxy type compounds, such as2,2-azobisisobutyronitrile (VAZO 64) (AIBN), 4,4-azobis(4-cyanovalericacid), 1,1-azobis(cyclohexanecarbonitrile), benzoyl peroxide,1,1-bis(tert-butylperoxy)cyclohexane, tert-butyl hydroperoxide,tert-butyl peroxybenzoate and dicumyl peroxide. Generally, the amount ofthermal initiator can range from about 0.05% w/w to about 5% w/w andtypically from about 0.1% w/w to about 1% w/w.

An organic diluent (solvent) can be included in any one composition ofinterest. As used herein, the term “organic diluent” encompasses organiccompounds which minimize incompatibility of the components in theinitial monomeric mixture and are substantially nonreactive with thecomponents in the initial mixture. Additionally, the organic diluentserves to minimize phase separation of polymerized products produced bypolymerization of the monomeric mixture. Also, the organic diluent willgenerally be relatively non-flammable. Contemplated organic diluentsinclude alcohols such as tert-butanol (TBA), tert-amyl alcohol, diols,such as ethylene glycol; and polyols, such as glycerol. Typically, theorganic diluent is water soluble and can be removed easily through awater extraction process. Other suitable organic diluents would beapparent to a person of ordinary skill in the art.

The organic diluent is included in an amount effective to provide thedesired effect (for example, minimal phase separation of polymerizedproducts). Generally, the diluent is included at 0 to 60% by weight ofthe monomeric mixture, with about 1% to about 40% by weight being moretypical, about 2% to about 30% by weight being even more typical andabout 3% to about 25% by weight being especially typical.

The compositions described can also include at least one UV absorbingcompound. Surprisingly, UV absorbing compounds can have a substantiallydifferent impact on the reaction kinetics of the reactive components inthe reaction mixtures of the present invention. For example, it has beenfound that benzotriazoles substantially slow the rate of reaction forNVP and TEGDMA is some systems much more than the reaction rates of thesilicone-containing components. In the case of NVP, this can bebeneficial, as it can provide additional processing flexibility and anexceptional balance of properties, including water contents in excess ofabout 60%, haze values less than about 50%, or less than about 10%,advancing contact angles less than about 60° and Dk's greater than about80.

When the silicone hydrogel is used as an ophthalmic device it may bedesirable to incorporate a reactive UV absorbing compound in thereaction mixture so that the resulting silicone hydrogel will be UVabsorbing. However, in another embodiment nonreactive UV absorbingcompounds may be used solely to achieve the desired reaction kinetics.Alternatively, solution filters may be used. It is believed that the UVabsorbers in the reactive mixtures block incident light below about 370nm which alters the spectrum of light being imposed on the visiblephotoinitiator. This tends to reduce the rate of initiation as well aslower the concentration of initiator radicals present, which in turn isbelieved to have a significant impact on the rate of polymerization ofthe monomers. Typically, the monomers which are likely to be mostsignificantly impacted are the slowest and fastest. In several of theexamples included herein, NVP (slowest) and TEGDMA (the fastest) are themost sensitive to the presence of the UV absorber.

Suitable UV absorbers may be derived from2-(2′-hydroxyphenyl)benzotriazoles, 2-hydroxybenzophenones,2-hydroxyphenyltriazines, oxanilides, cyanoacrylates, salicylates and4-hydroxybenzoates; which may be further reacted to incorporate reactivepolymerizable groups, such as (meth)acrylates. Specific examples of UVabsorbers which include polymerizable groups include2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole (Norbloc),5-vinyl and 5-isopropenyl derivatives of2-(2,4-dihydroxyphenyl)-2H-benzotriazole and 4-acrylates or4-methacrylates of 2-(2,4-dihydroxyphenyl)-2H-benzotriazole or2-(2,4-dihydroxyphenyl)-1,3-2H-dibenzotriazole, mixtures thereof and thelike. When a UV absorber is included, it may be included in amountsbetween about 0.5% and about 4% by weight, and suitably between about 1%and about 2% by weight.

The present invention relates to monomeric formulations useful in themanufacture of biocompatible medical devices. More particularly, thepresent invention relates to hydrogel formulations capable ofpolymerization to form polymeric compositions having desirable physicalproperties useful in the manufacture of contact lenses. Such propertiesmay include low modulus of elasticity, a high level of oxygenpermeability, wettability, lubricity and a low level of extractables.

According to the present process, the non-silicone and siliconcontaining monomeric mixture, comprising at least one hydrophilicmonomer, and an optionally the organic diluent, is shaped and cured byconventional methods such as static casting or spincasting. Thecross-linking agent(s) is useful for a wide variety of polymericmaterials, either rigid or soft. Especially typical polymeric materialsare lenses including contact lenses, phakic and aphakic intraocularlenses and corneal implants although all polymeric materials includingbiomaterials are contemplated as being within the scope of thisinvention. Typical articles are optically clear and useful as a contactlens.

The cross-linking agent(s) can be prepared by a variety of syntheticroutes. Moreover, many of the cross-linking agent(s) can be stable andnon-volatile under common polymerization conditions used in the art. Inone embodiment, the reaction of 1-vinylpyrrolidin-2-one-3-carboxylicacid with hydroxyethylmethacrylate (HEMA) will result in cross-linkingagent (1). See, Scheme 1.

In another embodiment, the reaction of 1-vinylpyrrolidin-2-one withoxirane or an alkyl halide, followed by a reaction with an acyl chloridewill result in cross-linking agent (4). See, Scheme 2.

Other embodiments are shown in the examples below. In general, andwithout being limited thereto, synthesis can include reacting acarbanion of the N-vinylpyrrolidin-2-one (e.g. nucleophile) with anelectrophile (e.g. oxirane or alkyl halide) followed by esterification;reacting an N-vinylpyrrolidin-2-one having a leaving group (on a ringcarbon) with a nucleophile (e.g. amine/amide or alcohol); or reacting acarboxylic acid substituted N-vinylpyrrolidin-2-one-3-carboxylic acidwith an alcohol or amide. One skilled in the art would understand thevarious substituted substrates that may be used.

Lens formation can be by free radical polymerization such asazobisisobutyronitrile (AIBN) and peroxide catalysts using initiatorsand under conditions such as those set forth in U.S. Pat. No. 3,808,179,incorporated herein by reference. Photoinitiation of polymerization ofthe monomer mixture as is well known in the art may also be used in theprocess of forming an article as disclosed herein. Following hydration,the shaped article, for example a lens for custom optics lens, isoptionally machined by various processes known in the art. The machiningstep includes lathe cutting a lens surface, lathe cutting a lens edge,buffing a lens edge or polishing a lens edge or surface. The presentprocess is particularly advantageous for processes wherein a lenssurface is lathe cut, since machining of a lens surface is especiallydifficult when the surface is tacky or rubbery. The described hydrogelmaterials can also be prepared by film casting.

The examples should not be read as limiting the scope of the inventionas defined in the claims. Unless clearly stated otherwise all numericalpercentages, e.g., percentage amounts of monomer in a polymerizationmixture, are listed as weight percent, supra.

The compositions described herein can be used to make hydrogel materialsfor a biomedical device such as artificial heart valves, films, surgicaldevices, vessel substitutes, intrauterine devices, membranes,diaphragms, surgical implants, artificial blood vessels, artificialureters, artificial breast tissue and membranes intended to come intocontact with body fluid outside of the body, e.g., membranes for kidneydialysis and heart/lung machines and the like, catheters, mouth guards,denture liners, ophthalmic devices, and especially hydrogel contactlenses.

As used herein, a “biomedical device” is any article that is designed tobe used while either in or on mammalian tissues or fluid, and in oneembodiment in or on human tissue or fluids. Examples of these devicesinclude but are not limited to catheters, implants, stents, andophthalmic devices such as intraocular lenses, punctal plugs and contactlenses.

The transitional term “comprising”, which is synonymous with“including,” “containing,” or “characterized by,” is inclusive oropen-ended and does not exclude additional, unrecited elements or methodsteps. The transitional phrase “consisting of” excludes any element,step, or ingredient not specified in the claim. The transitional phrase“consisting essentially of” limits the scope of a claim to the specifiedmaterials or steps “and those that do not materially affect the basicand novel characteristic(s)” of the claimed invention.

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities, percentages orproportions, and other numerical values used in the specification andclaims, are to be understood as being modified in all instances by theterm “about.” Furthermore, all ranges disclosed herein are inclusive ofthe endpoints and are independently combinable. Whenever a numericalrange with a lower limit and an upper limit are disclosed, any numberfalling within the range is also specifically disclosed.

Any term, abbreviation or shorthand not defined is understood to havethe ordinary meaning used by a person skilled in the art at the time theapplication is filed. The singular forms “a,” “an,” and “the,” includeplural references unless expressly and unequivocally limited to oneinstance.

EXAMPLES

All monomer components (both silicone and hydrophilic monomers) werepurified before use. Mechanical properties were determined on samplesstored in BBS using ASTM Instron methods. Oxygen permeability valueswere measured using the polarographic probe method. Films were preparedvia polymerization between treated glass plates having a suitable inertspacer. The films were extracted in distilled water and/or in2-propanol, hydrated in borate-buffered saline (pH 7.3) and autoclavedfor 30 minutes. Wetting angle was performed via the captive bubbletechniques. All of the above methods and analytical techniques are wellknown to a person of ordinary skill in the art.

Example 1: Synthesis of Cross-Linking Agent (1)

In a dry 250 mL round bottom flask was added the1-vinylpyrrolidin-2-one-3-carboxylic acid (1.6 g, 10.3 mmol), diluted in40 mL of dichloromethane (DCM), and then hydroxyethylmethacrylate (HEMA)(1.4 g, 10.7 mmol, 1.05 eq.) was added and the solution was stirred for15 minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDAC·HCl) (2.35 g, 12.2 mmol, 1.2 eq.) was then added and the solutionwas stirred for 1 h at room temperature and monitored by HPLC. Water (25mL) was then added to the solution and the organic layer was separated.The organic layer was then washed with water (3×25 mL), and then driedwith Na₂SO₄, filtered, and solvent was evaporated to give a crudeproduct as yellow oil. The yellow oil was then purified by columnchromatography (0 to 10% DCM/EtOAc) to afford the crosslinker as acolorless oil (78%). The HPLC purity was determined at 97% and the NMRspectrum conforms to the structure (1): ¹H-NMR (CDCl₃): 7.05 (1H, dd,J=9, 16 Hz), 6.15 (1H, s), 5.62-5.59 (1H, m), 4.56-4.37 (6H, m),3.70-3.63 (1H, m), 3.59 (1H, dd, J=7, 10 Hz), 3.55-3.48 (1H, m),2.55-2.45 (1H, m), 2.43-2.33 (1H, m).

Example 1A: Synthesis of Cross-Linking Agent (2)

In a dry 250 mL round bottom flask was added the1-vinylpyrrolidin-2-one-3-carboxylic acid (1 g, 6.44 mmol), diluted in40 mL of dichloromethane (DCM), and then 6-hydroxyhexyl methacrylate(1.21 g, 6.44 mmol, 1.0 eq.) was added and the solution was stirred for15 minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDAC·HCl) (1.39 g, 7.25 mmol, 1.12 eq.) was then added and the solutionwas stirred for 1 h at room temperature and monitored by HPLC. Water (40mL) was then added to the solution and the organic layer was separated.The organic layer was then washed with water (3×40 mL), and then driedwith Na₂SO₄, filtered, and solvent was evaporated to give a crudeproduct as yellow solid. The yellow solid was then purified by columnchromatography to afford the crosslinker as off white solid (71%). TheHPLC purity was determined at 97% and the NMR spectrum conforms to thestructure (2): ¹H-NMR (CDCl₃): 6.9 (1H, dd), 6.4 (1H, s), 6.48 (1H, s)5.8 (1H, s), 4.2 (1H, s), 4.1 (2H, t), 3.9 (2H, t), 3.5-3.6 (4H, m),3.06 (1H, s), 2.1 (3H, s), 1.62-1.43 (8H, m)

Example 1B: Synthesis of Cross-Linking Agent (3)

In a dry 250 mL round bottom flask was added the1-vinylpyrrolidin-2-one-3-carboxylic acid (1 g, 6.44 mmol), diluted in40 mL of dichloromethane (DCM), and then 2-aminoethyl methacrylate (1.07g, 6.44 mmol, 1.0 eq.) was added and the solution was stirred for 15minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDAC·HCl) (1.39 g, 7.25 mmol, 1.12 eq.) was then added and the solutionwas stirred for 1 h at room temperature and monitored by HPLC. Water (80mL) was then added to the solution and the organic layer was separated.The organic layer was then washed with water (3×70 mL), and then driedwith Na₂SO₄, filtered, and solvent was evaporated to give a crudeproduct as yellow solid. The yellow solid was then purified by columnchromatography to afford the crosslinker as off white solid (56%). TheHPLC purity was determined at 96% and the NMR spectrum conforms to thestructure (3): ¹H-NMR (CDCl₃): 8.03 (1H, s), 6.96 (1H, dd), 6.4 (1H, s),6.48 (1H, s) 5.78 (1H, m), 5.7-4.6 (1H, m), 4.3 (2H, t), 4.1 (2H, t),3.6-3.5 (4H, m), 3.06 (1H, s), 1.98 (3H, s)

Example 2. Hydrogel Contact Lenses Examples 2A and 2B

Hydrogel contact lenses were prepared from each formulation examples 2Aand 2B. The contact lenses were prepared from a monomer formulation thatincludes hydroxyethylmethacrylate (HEMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (1) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (1) are shown in Table 1:

TABLE 1 2A (wt %) 2B (wt %) HEMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING 0.5 0.5 AGENT (1) TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 2C and 2D

Hydrogel contact lenses were prepared from each formulation examples 2Cand 2D. The contact lenses were prepared from a monomer formulation thatincludes glycidyl methacrylate (GMMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (1) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (1) are shown in Table 2:

TABLE 2 2C (wt %) 2D (wt %) GMMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING 0.5 0.5 AGENT (1) TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Example 2E and 2F

Hydrogel contact lenses were prepared from each formulation examples 2Eand 2F. The contact lenses were prepared from a monomer formulation thatincludes dimethylacrylamide (DMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (1) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (1) are shown in Table 3:

TABLE 3 2E (wt %) 2F (wt %) DMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING 0.5 0.5 AGENT (1) TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 2G and 2H

Hydrogel contact lenses were prepared from formulation examples 2G and2H. The contact lenses were prepared from a monomer formulation thatincludes 3-(tris-(trimethylsiloxy)silyl)propyl methacrylate (TRIS),1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate (EGDMA),cross-linking agent (1) and diphenyl(2,4,6-trimethylbenzoyl)phosphineoxide (TPO). The amounts of the monomers and cross-linking agent (1) areshown in Table 4:

TABLE 4 2G (wt %) 2H (wt %) TRIS 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING 0.5 0.5 AGENT (1) TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 2I and 2J

Hydrogel contact lenses were prepared from formulation examples 2I and2J. The contact lenses were prepared from a monomer formulation thatincludes3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane(SIGMA), 1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate(EGDMA), cross-linking agent (1) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (1) are shown in Table 5:

TABLE 5 2I (wt %) 2J (wt %) SIGMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING 0.5 0.5 AGENT (1) TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

TABLE 6 Mechanical Properties of Examples 2A to 2F and 2H Property 2A 2B2C 2D 2E 2F 2H % Ext. 0.9 5 8 6.7 9 6.5 10 5 Saline Modulus MPa 0.330.42 0.41 0.50 0.39 0.45 0.45 Tear N/mm 0.08 0.07 0.08 Water 50.3 68 4570 57 71 48.3 Content (IPA Ext. Only) Contact Angle 44 41 40 — 44 — 37Hardness — — — — — — —

Examples 2K and 2L

Hydrogel contact lenses were prepared from each formulation examples 2Kand 2L. The contact lenses were prepared from a monomer formulation thatincludes hydroxyethylmethacrylate (HEMA), 1-Vinyl-2-pyrrolidinone (NVP),poly(ethylene glycol) diacrylate) (pEGDA), cross-linking agent (1) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (1) are shown in Table 7:

TABLE 7 2K (wt %) 2L (wt %) HEMA 79.5 45 NVP 19.0 53.5 pEGDA 0.5 0.5CROSS-LINKING 0.5 0.5 AGENT (1) TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Example 2M, 2N, 2O, 2P

Hydrogel contact lenses were prepared from formulation examples 2M, 2N,2O and 2P. The contact lenses were prepared from a monomer formulationthat includes hydroxyethylmethacrylate, 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (1) andethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L). The amounts ofthe monomers and cross-linking agent (1) are shown in Table 8:

TABLE 8 2M 2N 2O 2P (wt %) (wt %) (wt %) (wt %) HEMA 68.45 58.45 57.6557.95 NVP 30 40 40 40 EGDMA 0.5 0.5 0.9 0.9 CROSS-LINKING 0.5 0.5 0.90.6 AGENT (1) TPO-L 0.5 0.55 0.55 0.55

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 3A and 3B

Hydrogel contact lenses were prepared from formulation examples 3A and3B. The contact lenses were prepared from a monomer formulation thatincludes 3-(tris-(trimethylsiloxy)silyl)propyl methacrylate (TRIS),1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate (EGDMA),cross-linking agent (2) and diphenyl(2,4,6-trimethylbenzoyl)phosphineoxide (TPO). The amounts of the monomers and cross-linking agent (2) areshown in Table 9:

TABLE 9 3A (wt %) 3B (wt %) TRIS 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 3C and 3D

Hydrogel contact lenses were prepared from formulation examples 3C and3D. The contact lenses were prepared from a monomer formulation thatincludes 3-(tris-(trimethylsiloxy)silyl)propyl methacrylate (TRIS),1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate (EGDMA),cross-linking agent (2) and azobisisobutyronitrile (AIBN). The amountsof the monomers and cross-linking agent (2) are shown in Table 10:

TABLE 10 3C (wt %) 3D (wt %) TRIS 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.3 0.3 AIBN 0.7 0.7

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 15 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an oven for 15 minutes at 60° C. The oventemperature was ramped up to 90° C. over 2 h at 5° C. per 5 minutes. Themolds were then left for 4 h at 90° C.

The lenses were removed from the oven and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 3E and 3F

Hydrogel contact lenses were prepared from each formulation examples 3Eand 3F. The contact lenses were prepared from a monomer formulation thatincludes hydroxyethylmethacrylate (HEMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (2) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (2) are shown in Table 11:

TABLE 11 3E (wt %) 3F (wt %) HEMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 3G and 3H

Hydrogel contact lenses were prepared from each formulation examples 3Gand 3H. The contact lenses were prepared from a monomer formulation thatincludes hydroxyethylmethacrylate (HEMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (2) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (2) are shown in Table 12:

TABLE 12 3G (wt %) 3H (wt %) HEMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 15 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an oven for 15 minutes at 60° C. The oventemperature was ramped up to 90° C. over 2 h at 5° C. per 5 minutes. Themolds were then left for 4 h at 90° C.

The lenses were removed from the oven and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 3I and 3J

Hydrogel contact lenses were prepared from each formulation examples 3Iand 3J. The contact lenses were prepared from a monomer formulation thatincludes glycidyl methacrylate (GMMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (2) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (2) are shown in Table 13:

TABLE 13 3I (wt %) 3J (wt %) GMMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 3K and 3L

Hydrogel contact lenses were prepared from formulation examples 3K and3L. The contact lenses were prepared from a monomer formulation thatincludes3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane(SIGMA), 1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate(EGDMA), cross-linking agent (2) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (2) are shown in Table 14:

TABLE 14 3K(wt %) 3L (wt %) SIGMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 3M and 3N

Hydrogel contact lenses were prepared from formulation examples 3M and3N. The contact lenses were prepared from a monomer formulation thatincludes3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane(SIGMA), 1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate(EGDMA), cross-linking agent (2) and azobisisobutyronitrile (AIBN). Theamounts of the monomers and cross-linking agent (2) are shown in Table15:

TABLE 15 3M (wt %) 3N (wt %) SIGMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.3 0.3 AIBN 0.7 0.7

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 15 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an oven for 15 minutes at 60° C. The oventemperature was ramped up to 90° C. over 2 h at 5° C. per 5 minutes. Themolds were then left for 4 h at 90° C.

The lenses were removed from the oven and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 4A and 4B

Hydrogel contact lenses were prepared from formulation examples 4A and4B. The contact lenses were prepared from a monomer formulation thatincludes 3-(tris-(trimethylsiloxy)silyl)propyl methacrylate (TRIS),1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate (EGDMA),cross-linking agent (3) and diphenyl(2,4,6-trimethylbenzoyl)phosphineoxide (TPO). The amounts of the monomers and cross-linking agent (3) areshown in Table 16:

TABLE 16 4A (wt %) 4B (wt %) TRIS 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (3) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 4C and 4D

Hydrogel contact lenses were prepared from formulation examples 4C and4D. The contact lenses were prepared from a monomer formulation thatincludes 3-(tris-(trimethylsiloxy)silyl)propyl methacrylate (TRIS),1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate (EGDMA),cross-linking agent (3) and azobisisobutyronitrile (AIBN). The amountsof the monomers and cross-linking agent (3) are shown in Table 17:

TABLE 17 4C (wt %) 4D (wt %) TRIS 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (3) 0.3 0.3 AIBN 0.7 0.7

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 15 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an oven for 15 minutes at 60° C. The oventemperature was ramped up to 90° C. over 2 h at 5° C. per 5 minutes. Themolds were then left for 4 h at 90° C.

The lenses were removed from the oven and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 4E and 4F

Hydrogel contact lenses were prepared from each formulation examples 4Eand 4F. The contact lenses were prepared from a monomer formulation thatincludes hydroxyethylmethacrylate (HEMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (3) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (3) are shown in Table 18:

TABLE 18 4E (wt %) 4F (wt %) HEMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (3) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 4G and 4H

Hydrogel contact lenses were prepared from each formulation examples 4Gand 4H. The contact lenses were prepared from a monomer formulation thatincludes hydroxyethylmethacrylate (HEMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (3) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (3) are shown in Table 19:

TABLE 19 4G (wt %) 4H (wt %) HEMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (3) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 15 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an oven for 15 minutes at 60° C. The oventemperature was ramped up to 90° C. over 2 h at 5° C. per 5 minutes. Themolds were then left for 4 h at 90° C.

The lenses were removed from the oven and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 4I and 4J

Hydrogel contact lenses were prepared from each formulation examples 4Iand 4J. The contact lenses were prepared from a monomer formulation thatincludes glycidyl methacrylate (GMMA), 1-Vinyl-2-pyrrolidinone (NVP),ethylene glycol dimethacrylate (EGDMA), cross-linking agent (3) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (3) are shown in Table 20:

TABLE 20 4I (wt %) 4J (wt %) GMMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (2) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 4K and 4L

Hydrogel contact lenses were prepared from formulation examples 4K and4L. The contact lenses were prepared from a monomer formulation thatincludes3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane(SIGMA), 1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate(EGDMA), cross-linking agent (3) anddiphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). The amounts ofthe monomers and cross-linking agent (3) are shown in Table 21:

TABLE 21 4K (wt %) 4L (wt %) SIGMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (3) 0.5 0.5 TPO 0.5 0.5

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 10 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an UV chamber for 15 minutes.

The lenses were removed from the UV-chamber and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

Examples 4M and 4N

Hydrogel contact lenses were prepared from formulation examples 4M and4N. The contact lenses were prepared from a monomer formulation thatincludes3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane(SIGMA), 1-Vinyl-2-pyrrolidinone (NVP), ethylene glycol dimethacrylate(EGDMA), cross-linking agent (3) and azobisisobutyronitrile (AIBN). Theamounts of the monomers and cross-linking agent (3) are shown in Table22:

TABLE 22 4M (wt %) 4N (wt %) SIGMA 79.5 45 NVP 19.0 53.5 EGDMA 0.5 0.5CROSS-LINKING AGENT (3) 0.3 0.3 AIBN 0.7 0.7

The monomer formulation mixture was mixed well using magnetic stirrerand then degassed for 15 minutes using dry nitrogen stream. The mixedformulation was added to unpurged polypropylene lens molds, and thefilled molds were placed in an oven for 15 minutes at 60° C. The oventemperature was ramped up to 90° C. over 2 h at 5° C. per 5 minutes. Themolds were then left for 4 h at 90° C.

The lenses were removed from the oven and allowed to cool to roomtemperature. The lenses were dry released from the molds. Alternatively,the lenses can be wet released from the mold. Dry release or wet releasemethods are well known to those of ordinary skill in the contact lensart.

This written description uses examples to disclose the invention,including the best mode, and also to enable any person skilled in theart to make and use the invention. Many modifications of the exemplaryembodiments of the invention disclosed above will readily occur to thoseskilled in the art. Accordingly, the invention is to be construed asincluding all structure and methods that fall within the scope of theappended claims. Unless otherwise specified, the recitation of a genusof elements, materials or other components, from which an individualcomponent or mixture of components can be selected, is intended toinclude all possible sub-generic combinations of the listed componentsand mixtures thereof.

We claim:
 1. A compound of formula I:

R¹-R¹¹ are the same or different, and are each independently selectedfrom H, halo, hydroxyl, a substituted or unsubstituted hydrocarbongroup, a substituted or unsubstituted heterogeneous group, a substitutedor unsubstituted carbocyclic group, a substituted or unsubstitutedheterocyclic group, a substituted or unsubstituted aromatic group, asubstituted or unsubstituted heteroaromatic group, or NR^(a)R^(b),wherein R^(a) and R^(b) are the same or different, and are independentlyselected from H, halo, hydroxyl, amino, a substituted or unsubstitutedhydrocarbon group, a substituted or unsubstituted heterogeneous group, asubstituted or unsubstituted carbocyclic group, a substituted orunsubstituted heterocyclic group, a substituted or unsubstitutedaromatic group, or a substituted or unsubstituted heteroaromatic group;X¹ is selected from NR^(a), NR^(a)C(O), OC(O)NR^(a), NR^(a)C(O)O,NR^(a)C(O)NH, NHC(O)NR^(a), OC(O), NHC(O)NHZ₀—NH—C(O)NH,OC(O)NHZ₀—NH—C(O)O, OC(O)NHZ₀—NH—C(O)NH, or NHC(O)NHZ₀—NH—C(O)O; whereZ₀ is a linear or branched C₂-C₁₂ alkylene divalent radical, or a C₅-C₇cycloaliphatic divalent radical, each of which can optionally includeone or more linkages of O, NR^(a) and C(O); X² is selected from a directbond, a heteroatom, C(O), a substituted or unsubstituted hydrocarbongroup, a substituted or unsubstituted heterogeneous group, a substitutedor unsubstituted carbocyclic group, a substituted or unsubstitutedheterocyclic group, a substituted or unsubstituted aromatic group, asubstituted or unsubstituted heteroaromatic group, or NR^(a); and Z isselected from a heteroatom, C(O), a substituted or unsubstitutedhydrocarbon group, a substituted or unsubstituted heterogeneous group, asubstituted or unsubstituted carbocyclic group, a substituted orunsubstituted heterocyclic group, a substituted or unsubstitutedaromatic group, a substituted or unsubstituted heteroaromatic group,NR^(a), or [SiR¹²R¹³O]_(w)SiR¹²R¹³, wherein R¹² and R¹³ are the same ordifferent, and are independently selected from H, halo, hydroxyl, amino,a substituted or unsubstituted hydrocarbon group, a substituted orunsubstituted heterogeneous group, a substituted or unsubstitutedcarbocyclic group, a substituted or unsubstituted heterocyclic group, asubstituted or unsubstituted aromatic group, or a substituted orunsubstituted heteroaromatic group, and w is from 0 to
 60. 2. Thecompound of claim 1, wherein R¹-R¹¹ are the same or different, and areeach independently selected from H, halo, hydroxyl, a substituted orunsubstituted hydrocarbon group, or a substituted or unsubstitutedheterogeneous group.
 3. The compound of claim 2, wherein R¹-R¹¹ are thesame or different, and are each independently selected from H, halo,hydroxyl, a substituted or unsubstituted C₁-C₆ alkyl, a substituted orunsubstituted C₁-C₆ alkoxy, or a substituted or unsubstituted C₁-C₆alkanol.
 4. The compound of claim 2, wherein R¹-R¹¹ are the same ordifferent, and are each independently selected from H or a substitutedor unsubstituted hydrocarbon group.
 5. The compound of claim 4, whereinR¹-R¹¹ are the same or different, and are each independently selectedfrom H or a substituted or unsubstituted alkyl group.
 6. The compound ofclaim 5, wherein R¹-R¹¹ are the same or different, and are eachindependently selected from H or a substituted or unsubstituted C₁-C₆alkyl.
 7. The compound of claim 6, wherein R¹-R¹¹ are the same ordifferent, and are each independently selected from H or unsubstitutedC₁-C₆ alkyl.
 8. The compound of claim 7, wherein R¹-R¹¹ are the same ordifferent, and are each independently selected from H or methyl.
 9. Thecompound of claim 1, wherein R¹, R², R¹⁰, and R¹¹ are H.
 10. Thecompound of claim 1, wherein X² is selected from a direct bond, O,NR^(a), C(O), C(O)NR^(a), NR^(a)C(O), OC(O)NR^(a), NR^(a)C(O)O,NR^(a)C(O)NH, NHC(O)NR^(a), C(O)O, OC(O), NHC(O)NHZ₀—NH—C(O)NH,OC(O)NHZ₀—NH—C(O)O, OC(O)NHZ₀—NH—C(O)NH, or NHC(O)NHZ₀—NH—C(O)O; whereZ₀ is a linear or branched C₂-C₁₂ alkylene divalent radical, or a C₅-C₇cycloaliphatic divalent radical, each of which can optionally includeone or more linkages of O, NR^(a) and C(O).
 11. The compound of claim 1,wherein X¹ is selected from NR^(a), NR^(a)C(O), NR^(a)C(O)O,OC(O)NR^(a), NR^(a)C(O)O, or OC(O) and X² is selected from a directbond, O, NR^(a), C(O), C(O)NR^(a), NR^(a)C(O), NR^(a)C(O), OC(O)NR^(a),NR^(a)C(O)O, C(O)O, or OC(O).
 12. The compound of claim 11, wherein X¹is selected from NR^(a), NR^(a)C(O), NR^(a)C(O)O, OC(O)NR^(a), orNR^(a)C(O)O and X² is selected from a direct bond, O, NR^(a), C(O),C(O)NR^(a), NR^(a)C(O), NR^(a)C(O), OC(O)NR^(a), NR^(a)C(O)O, C(O)O, orOC(O), wherein R^(a) is selected from H or a substituted orunsubstituted hydrocarbon group.
 13. The compound of claim 12, whereinR^(a) is selected from H or unsubstituted C₁-C₆ alkyl.
 14. The compoundof claim 13, wherein R^(a) is selected from H or methyl.
 15. Thecompound of claim 10, wherein X² is selected from a direct bond, O, orNR^(a).
 16. The compound of claim 1, wherein Z is selected from a directbond, a substituted or unsubstituted hydrocarbon group, a substituted orunsubstituted heterogeneous group, or [SiR¹²R¹³O]_(w)SiR¹²R₁₃.
 17. Thecompound of claim 1, wherein Z is selected from a direct bond, asubstituted or unsubstituted hydrocarbon group, a substituted orunsubstituted heterogeneous group, or [SiR¹²R¹³O]_(w)SiR¹²R¹³, whereinR¹² and R¹³ are the same or different, and are independently selectedfrom C₁-C₄ alkyl or phenyl, and w is from 0 to
 60. 18. The compound ofclaim 1, wherein Z is selected from a direct bond, or a substituted orunsubstituted hydrocarbon group.
 19. The compound of claim 1, wherein Zis selected from a substituted or unsubstituted hydrocarbon group. 20.The compound of claim 19, wherein Z is selected from a substituted orunsubstituted alkyl group.
 21. The compound of claim 19, wherein Z isselected from a substituted or unsubstituted C₁-C₂₀ alkyl.
 22. Thecompound of claim 19, wherein Z is selected from a substituted orunsubstituted C₁-C₆ alkyl.
 23. The compound of claim 19, wherein Z isselected from an unsubstituted C₁-C₆ alkyl.
 24. The compound of claim 1,wherein Z is selected from a substituted or unsubstituted aromaticgroup.
 25. The compound of claim 24, wherein Z is selected from asubstituted or unsubstituted phenyl group.
 26. The compound of claim 1,wherein Z is selected from a C₁-C₁₂ unsubstituted or substituted, linearor branched alkylene divalent radical, where each alkylene divalentradical can optionally include one or more linkages of O, NR^(a), andC(O), an unsubstituted phenylene divalent radical, a C₅-C₇cycloaliphatic divalent radical, or a C₇-C₁₂ arylalkylene divalentradical.
 27. The compound of claim 1, wherein the compound is a dualreactive cross-linking agent(s).
 28. A composition comprising one ormore of the compounds of claim
 1. 29. A cross-linking agent comprisingone or more of the compounds of claim
 1. 30. A biocompatible medicaldevice comprising one or more of the compounds of claim
 1. 31. A methodof producing biocompatible medical devices(s), the method comprisingreacting at least one of the compounds of claim 1 with at least onemonomer.
 32. A composition comprising at least one (meth)acrylicmonomer, at east one vinyl containing monomer and at least one of thecompounds of claim
 1. 33. The composition of claim 32, wherein the atleast one vinyl containing monomer comprises at least one siliconemonomer.
 34. The composition of claim 33 wherein the silicone monomer isselected from the group consisting oftris-(trimethylsiloxy)-3-methacryloxypropyl methacrylate (Tris),3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane (Sigma), or a mixture thereof.35. The composition of claim 32, wherein the at least one vinylcontaining monomer is selected from hydroxyethylmethacrylate (HEMA),glycidyl methacrylate (GMMA), dimethylacrylamide (DMA),3-(tris-(trimethylsiloxy)silyl)propyl methacrylate (TRIS),hydroxypropyloxy)propylbis(trimethylsiloxy)-methylsilane (SIGMA), orcombinations thereof.
 36. The composition of claim 32, wherein the atleast one vinyl monomer is selected from N-vinyl-2-pyrrolidone, N-vinylpiperidone, N-vinyl-caprolactam, N-vinylimidazolidone,N-vinylsuccinimide, N-vinylformamide, N-vinyl urea, N-vinylcarbamate,0-vinyl carbonate, 1-Vinyl-2-pyrrolidinone (NVP) or combinationsthereof.
 37. The composition of claim 36 wherein the at least one(meth)acrylic monomer includes4-t-butyl-2-hydroxycyclohexylmethacrylate, and the at least one vinylmonomer includes N-vinyl-2-pyrrolidone.
 38. The composition of claim 32,wherein the at least one (meth)acrylic monomer includes a functionalmonomer selected from the group consisting of carboxybetaines,sulfobetains and phosphobetaines.
 39. The composition of claim 38,wherein the functional monomer is selected from the group consisting ofmethacryloxy phosphatidyl choline (MPC), N-vinylcarboxy ethylphosphatidyl choline, 0-vinyl ethyl phosphatidyl choline carbonate,1-(3-sulfopropyl)-2-vinylpyridinium betaine, and3-dimethyl(acryloyloxyethyl) ammonium propyl sulfonate.
 40. Thecomposition of claim 32, further comprising at least one photoinitiator.41. The composition of claim 32, further comprising at least one(meth)acrylate cross-linking agent.
 42. The composition of claim 35wherein the Tris, Sigma or the combination thereof is present from about8% to about 30% by weight.
 43. The composition of claim 32, wherein theat least one compound is present from about 0.02% to about 0.4% byweight.
 44. A hydrogel polymer prepared from the composition of claim28.
 45. The hydrogel polymer of claim 44, wherein the polymer possessesa water content of at least about 40% by weight.
 46. The hydrogelpolymer of claim 44, wherein the polymer possesses a modulus ofelasticity of at least about 0.30 MPa.
 47. A contact lens prepared withthe hydrogel polymer of claim 44.